Cheng-He Zhou

Find an error

Name: 周成合; ChengGe Zhou

Organization: Southwest University

Department: Institute of Bioorganic & Medicinal Chemistry

Title: Professor

Chemicals
References

Novel Naphthalimide Aminothiazoles as Potential Multitargeting Antimicrobial Agents

Co-reporter:Ying-Ying Chen, Lavanya Gopala, Rammohan R. Yadav Bheemanaboina, Han-Bo Liu, Yu Cheng, Rong-Xia Geng, and Cheng-He Zhou

ACS Medicinal Chemistry Letters December 14, 2017 Volume 8(Issue 12) pp:1331-1331

Publication Date(Web):December 1, 2017

DOI:10.1021/acsmedchemlett.7b00452

A series of novel naphthalimide aminothiazoles were developed for the first time and evaluated for their antimicrobial activity. Some prepared compounds possessed good inhibitory activity against the tested bacteria and fungi. Noticeably, the piperazine derivative 4d displayed superior antibacterial activity against MRSA and Escherichia coli with MIC values of 4 and 8 μg/mL, respectively, to reference drugs. The most active compound 4d showed low toxicity against mammalian cells with no obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy and efficient membrane permeability. Preliminarily investigations revealed that compound 4d could not only bind with gyrase–DNA complex through hydrogen bonds but could effectively intercalate into MRSA DNA to form 4d–DNA supramolecular complex, which might be responsible for the powerful bioactivity. Further transportation behavior evaluation indicated that molecule 4d could be effectively stored and carried by human serum albumin, and the hydrophobic interactions and hydrogen bonds played important roles in the binding process.Keywords: aminothiazole; antibacterial; human serum albumin; MRSA DNA; Naphthalimide;

Discovery of potential antifungal triazoles: design, synthesis, biological evaluation, and preliminary antifungal mechanism exploration

Co-reporter:Yuan Zhang;Guri L. V. Damu;Sheng-Feng Cui;Jia-Li Mi;Vijai Kumar Reddy Tangadanchu

MedChemComm (2010-Present) 2017 vol. 8(Issue 8) pp:1631-1639

Publication Date(Web):2017/08/16

DOI:10.1039/C7MD00112F

A series of triazoles as miconazole analogues was designed, synthesized and characterized by IR, NMR, MS and HRMS. All the newly prepared compounds were screened for their antifungal activities against five kinds of fungi. The bioactive assay showed that most of the synthesized compounds exhibited good or even stronger antifungal activities in comparison with the reference drugs miconazole and fluconazole. In particular, the 3,4-dichlorobenzyl derivative 5b showed a comparable or superior activity against all the tested fungal strains to standard drugs, and formed a supramolecular complex with CYP51 via the hydrogen bond between the 4-nitrogen of the triazole nucleus and the histidine residue. Preliminary experiments revealed that both of the active molecules 5b and 9c could intercalate into calf thymus DNAs, which might block DNA replication to exhibit their powerful antifungal abilities. Further studies indicated that compound 5b might be stored and transported by human serum albumin through hydrophobic interactions, specific electrostatic interactions and hydrogen bonds. These results strongly suggested that compound 5b could serve as a promising antifungal candidate.

Novel benzimidazolyl tetrahydroprotoberberines: Design, synthesis, antimicrobial evaluation and multi-targeting exploration

Co-reporter:Ponmani Jeyakkumar, Han-Bo Liu, Lavanya Gopala, Yu Cheng, Xin-Mei Peng, Rong-Xia Geng, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 8(Issue 8) pp:

Publication Date(Web):15 April 2017

DOI:10.1016/j.bmcl.2017.02.071

A series of novel benzimidazolyl tetrahydroprotoberberines were conveniently designed and efficiently synthesized from berberine via direct cyclization of tetrahydroprotoberberine aldehyde and o-phenylene diamines under metal-free aerobic oxidation. All the new compounds were characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The antimicrobial evaluation revealed that the 5-fluorobenzimidazolyl derivative 5b was the most active antibacterial and antifungal molecule with broad spectrum in comparison to Berberine, Chloromycin, Norfloxacin and Fluconazole. It triggered almost no resistance development against MRSA even after 15 passages. Further studies demonstrated that compound 5b could not only effectively interact with Topo IA by hydrogen bonds, but also intercalate into calf thymus DNA and cleave pBR322 DNA, which might be responsible for its powerful bioactivities.Download high-res image (72KB)Download full-size image

Chalcone-Benzotriazole Conjugates as New Potential Antimicrobial Agents: Design, Synthesis, Biological Evaluation and Synergism with Clinical Drugs

Co-reporter:Hanbo Liu;Lavanya Gopala;Srinivasa Rao Avula;Ponmani Jeyakkumar;Xinmei Peng;Chenghe Zhou;Rongxia Geng

Chinese Journal of Chemistry 2017 Volume 35(Issue 4) pp:483-496

Publication Date(Web):2017/04/01

DOI:10.1002/cjoc.201600639

AbstractA series of chalcone-benzotriazole conjugates as new potential antimicrobial agents were synthesized and characterized by 1H NMR, 13C NMR, IR and HRMS spectra. Antimicrobial assay manifested that some target compounds gave moderate to good antibacterial and antifungal activities. The N-1 derived benzotriazole 5e and N-2 derived benzotriazole 6a exhibited valuable inhibitory efficacy against some tested strains. Especially, derivative 6a gave superior antifungal efficacies against C. utilis, S. cerevisiae and A. flavus (MIC=0.01, 0.02, 0.02 µmol/mL, respectively) to Fluconazole. The drug combination of compound 5e or 6a with antibacterial Chloromycin, Norfloxacin and antifungal Fluconazole respectively showed stronger antimicrobial efficiency with less dosage and broader antimicrobial spectrum than their separated use alone. The preliminary interaction with calf thymus DNA revealed that compound 6a could intercalate into DNA to form 6a-DNA supramolecular complex which might be a factor to exert its powerful bioactivity. Molecular docking study indicated strong binding of compound 6a with DNA gyrase. The structural parameters such as molecular orbital energy and molecular electrostatic potential of compound 6a were also investigated, which provided better understanding for its good antimicrobial activity.

Design, synthesis and antimicrobial evaluation of novel benzimidazole-incorporated sulfonamide analogues

Co-reporter:Hui-Zhen Zhang, Shi-Chao He, Yan-Jun Peng, Hai-Juan Zhang, Lavanya Gopala, Vijai Kumar Reddy Tangadanchu, Lin-Ling Gan, Cheng-He Zhou

European Journal of Medicinal Chemistry 2017 Volume 136(Volume 136) pp:

Publication Date(Web):18 August 2017

DOI:10.1016/j.ejmech.2017.04.077

•Novel series of potentially antimicrobial sulfonamide benzimidazoles were developed.•Intercalation mechanism into DNA was suggested by experiments and molecular docking study.•Effective transportation by HSA towards highly active compounds were revealed.•Molecular electrostatic potentiality was studied by full geometry optimizations.A novel series of benzimidazole-incorporated sulfonamide analogues were designed and synthesized with an effort to overcome the increasing antibiotic resistance. Compound 5c gave potent activities against Gram-positive bacteria and fungi, and 2,4-dichlorobenzyl derivative 5g showed good activities against Gram-negative bacteria. Both of these two active molecules 5c and 5g could effectively intercalate into calf thymus DNA to form compound−DNA complex respectively, which might block DNA replication to exert their powerful antimicrobial activity. Molecular docking experiments suggested that compounds 5c and 5g could insert into base-pairs of DNA hexamer duplex by the formation of hydrogen bonds with guanine of DNA. The transportation behavior of these highly active compounds by human serum albumin (HSA) demonstrated that the electrostatic interactions played major roles in the strong association of active compounds with HSA, and which was also confirmed by the full geometry calculation optimizations.A novel series of benzimidazole-incorporated sulfonamide analogues were developed and screened for their antimicrobial activities. Interaction with calf thymus DNA and molecular docking were investigated. Transportation behavior with HSA was explored and molecular electrostatic potentiality was studied by full geometry optimizations.Download high-res image (261KB)Download full-size image

Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: Design, synthesis and bioactive evaluation

Co-reporter:Xian-Fu Fang, Di Li, Vijai Kumar Reddy Tangadanchu, Lavanya Gopala, Wei-Wei Gao, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 22(Issue 22) pp:

Publication Date(Web):15 November 2017

DOI:10.1016/j.bmcl.2017.10.020

A series of novel potentially antifungal hybrids of 5-flucytosine and fluconazole were designed, synthesized and characterized by 1H NMR, 13C NMR, IR and HRMS spectra. Bioactive assay manifested that some prepared compounds showed moderate to good antifungal activities in comparison with fluconazole and 5-flucytosine. Remarkably, the 3,4-dichlorobenzyl hybrid 7h could inhibit the growth of C. albicans ATCC 90023 and clinical resistant strain C. albicans with MIC values of 0.008 and 0.02 mM, respectively. The active molecule 7h could not only rapidly kill C. albicans but also efficiently permeate membrane of C. albicans. Molecular docking study revealed that compound 7h could interact with the active site of CACYP51 through hydrogen bond. Quantum chemical studies were also performed to explain the high antifungal activity. Further preliminary mechanism research suggested that molecule 7h could intercalate into calf thymus DNA to form a steady supramolecular complex, which might block DNA replication to exert the powerful bioactivities.Download high-res image (213KB)Download full-size image

Discovery of novel nitroimidazole enols as Pseudomonas aeruginosa DNA cleavage agents

Co-reporter:Zhen-Zhen Li, Lavanya Gopala, Vijai Kumar Reddy Tangadanchu, Wei-Wei Gao, Cheng-He Zhou

Bioorganic & Medicinal Chemistry 2017 Volume 25, Issue 24(Issue 24) pp:

Publication Date(Web):15 December 2017

DOI:10.1016/j.bmc.2017.10.028

A series of nitroimidazole enols as new bacterial DNA-targeting agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. The antimicrobial screening revealed that 2-methoxyphenyl nitroimidazole enol 3i possessed stronger anti-P. aeruginosa efficacy (MIC = 0.10 μmol/mL) than reference drugs Norfloxacin and Metronidazole. Time-kill kinetic assay manifested that the active molecule 3i could rapidly kill the tested strains. Molecular docking indicated that the interactions between compound 3i and topoisomerase II were driven by hydrogen bonds. Quantum chemical study was also performed on 3i to understand the structural features essential for activity. Further research found that compound 3i was not able to effectively intercalate into bacterial DNA but could cleave DNA isolated from the standard P. aeruginosa strain, which might block DNA replication to exert the efficient bioactivities, and this active molecule was also able to be stored and carried by human serum albumin via hydrophobic interactions and hydrogen bonds.Download high-res image (68KB)Download full-size image

Novel 3-Aminothiazolquinolones: Design, Synthesis, Bioactive Evaluation, SARs, and Preliminary Antibacterial Mechanism

Co-reporter:Sheng-Feng Cui; Dinesh Addla

Journal of Medicinal Chemistry 2016 Volume 59(Issue 10) pp:4488-4510

Publication Date(Web):April 26, 2016

DOI:10.1021/acs.jmedchem.5b01678

A series of novel 3-aminothiazolquinolones as analogues of quinolone antibacterial agents were designed and synthesized in an effort to circumvent quinolone resistance. Among these 3-aminothiazolquinolones, 3-(2-aminothiazol-4-yl)-7-chloro-6-(pyrrolidin-1-yl) quinolone 12b exhibited potent antibacterial activity, low cytotoxicity to hepatocyte cells, strong inhibitory potency to DNA gyrase, and a broad antimicrobial spectrum including against multidrug-resistant strains. This active molecule 12b also induced bacterial resistance more slowly than norfloxacin. Analysis of structure–activity relationships (SARs) disclosed that the 2-aminothiazole fragment at the 3-position of quinolone plays an important role in exerting antibacterial activity. Molecular modeling and experimental investigation of aminothiazolquinolone 12b with DNA from a sensitive methicillin-resistant Staphylococcus aureus (MRSA) strain revealed that the possible antibacterial mechanism might be related to the formation of a compound 12b–Cu2+–DNA ternary complex in which the Cu2+ ion acts as a bridge between the backbone of 3-aminothiazolquinolone and the phosphate group of the nucleic acid.

Design, synthesis and biological evaluation of berberine-benzimidazole hybrids as new type of potentially DNA-targeting antimicrobial agents

Co-reporter:Ponmani Jeyakkumar, Ling Zhang, Srinivasa Rao Avula, Cheng-He Zhou

European Journal of Medicinal Chemistry 2016 Volume 122() pp:205-215

Publication Date(Web):21 October 2016

DOI:10.1016/j.ejmech.2016.06.031

•Berberine-benzimidazole hybrids as a new type of potential antimicrobial agents.•Pivotal antimicrobial potency and broad spectrum for some berberine–benzimidazoles.•Interaction of 5d with pET-28a plasmid revealed DNA-cleaving activity.•Compound 5d could effectively intercalate in to DNA.•Compound 5d could be effectively stored and carried by HSA.A series of novel berberine-benzimidazole derivatives were conveniently and efficiently synthesized and characterized by NMR, IR, MS and HRMS spectra. Most of the prepared compounds showed effective antimicrobial activities in contrast with clinical norfloxacin, chloromycin and fluconazole. Especially, compound 5d exhibited good anti-MRSA, anti-Escherichia coli, and anti-Salmonella typhi activity with low MIC values of 2–8 μg/mL, which were comparable or even superior to reference drugs. The preliminarily interactive investigation revealed that the most active compound 5d could effectively intercalate into DNA to form 5d-DNA complex and cleavage DNA by agarose gel electrophoresis experiments. It was also found that compound 5d was able to efficiently permeabilize the membranes of both Gram-positive (MRSA) and Gram-negative (E. coli DH52) bacteria. Experiments and molecular docking both showed that human serum albumin (HSA) could effectively transport compound 5d and hydrophobic interactions and hydrogen bonds play important roles in the association of compound 5d with HSA.A series of berberine–benzimidazole hybrids were synthesized and screened for their antimicrobial activities, further studies with pET-28a (Escherichia coli DNA), calf thymus DNA, human serum albumin and molecular docking simulation were investigated.

Multi-targeting exploration of new 2-aminothiazolyl quinolones: Synthesis, antimicrobial evaluation, interaction with DNA, combination with topoisomerase IV and penetrability into cells

Co-reporter:Yu Cheng, Srinivasa Rao Avula, Wei-Wei Gao, Dinesh Addla, Vijai Kumar Reddy Tangadanchu, Ling Zhang, Jian-Mei Lin, Cheng-He Zhou

European Journal of Medicinal Chemistry 2016 Volume 124() pp:935-945

Publication Date(Web):29 November 2016

DOI:10.1016/j.ejmech.2016.10.011

•New potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were developed.•Compound 10f exhibited strong activity against MRSA and B. typhi and low toxicity.•Bacterial resistance development induced by active molecule was slower than Norfloxacin.•Membrane activities and computational chemistry studies rationalized the high bioactivity.•Compound 10f could effectively intercalate into DNA.A series of new potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were designed, synthesized and characterized by 1H NMR, 13C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that some of the prepared compounds showed moderate to good antibacterial and antifungal activities. Noticeably, compound 10f could effectively inhibit the growth of B. typhi and MRSA with MIC values of 1 and 8 μg/mL, respectively. Experimental results revealed that compound 10f was membrane-active and had the ability to rapidly kill the tested strains and effectively prevent the development of bacterial resistance. Moreover, this compound also exhibited low toxicity against L929 cells. Molecular docking indicated that compound 10f could bind with topoisomerase IV–DNA complexes through hydrogen bonds and hydrophobic interactions. Quantum chemical studies were also performed on 10f to understand the structural features essential for activity. The preliminary mechanism research suggested that compound 10f could intercalate into calf thymus DNA to form a steady supramolecular complex which might block DNA replication to exert the powerful bioactivities.Potentially multi-targeting new 2-aminothiazolyl quinolones were developed and screened for their antimicrobial activities. Time–kill kinetic assay and antibacterial resistance development were investigated. Membrane permeabilization and DNA interaction were explored for the possible antibacterial mechanism.

Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents

Co-reporter:Ling Zhang, Dinesh Addla, Jeyakkumar Ponmani, Ao Wang, Dan Xie, Ya-Nan Wang, Shao-Lin Zhang, Rong-Xia Geng, Gui-Xin Cai, Shuo Li, Cheng-He Zhou

European Journal of Medicinal Chemistry 2016 Volume 111() pp:160-182

Publication Date(Web):23 March 2016

DOI:10.1016/j.ejmech.2016.01.052

•Prepared quinolones gave strong antimicrobial activity and broad spectrum.•Some compounds exhibited strong anti-MRSA activity.•Inducing bacterial resistance by target compound was much slower than clinical drugs.•Molecular modeling with DNA rationalized the high antibacterial activity.•Interactions of compound and DNA indicated a possible interaction mechanism.A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.A novel series of membrane active quinolone benzimidazoles were synthesized and screened for their antimicrobial activities. Molecular modeling and experimental investigation with DNA suggested the possible antibacterial mechanism.

Discovery of novel berberine imidazoles as safe antimicrobial agents by down regulating ROS generation

Co-reporter:Si-Qi Wen, Ponmani Jeyakkumar, Srinivasa Rao Avula, Ling Zhang, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2016 Volume 26(Issue 12) pp:2768-2773

Publication Date(Web):15 June 2016

DOI:10.1016/j.bmcl.2016.04.070

A series of novel berberine-based imidazole derivatives as new type of antimicrobial agents were developed and characterized. Most of them gave good antibacterial activity toward the Gram-positive and negative bacteria. Noticeably, imidazolyl berberine 3a exhibited low MIC value of 1 μg/mL against Eberthella typhosa, which was even superior to reference drugs berberine, chloromycin and norfloxacin. The cell toxicity and ROS generation assay indicated that compound 3a showed low cell toxicity. The interactive investigation by UV–vis spectroscopic method revealed that compound 3a could effectively intercalate into calf thymus DNA to form 3a–DNA complex which might further block DNA replication to exert the powerful antimicrobial activities. The binding behavior of compound 3a to DNA topoisomerase IB revealed that hydrogen bonds and electrostatic interactions played important roles in the association of compound 3a with DNA topoisomerase IB.

A green and convenient approach toward benzimidazole derivatives and their antimicrobial activity

Co-reporter:Jing Wen, Yun-Lei Luo, Hui-Zhen Zhang, Huan-Huan Zhao, Cheng-He Zhou, Gui-Xin Cai

Chinese Chemical Letters 2016 Volume 27(Issue 3) pp:391-394

Publication Date(Web):March 2016

DOI:10.1016/j.cclet.2015.12.014

N-Alkylated benzimidazole derivatives have been synthesized via the aza-Michael addition reactions of 1H-benzimidazoles to α,β-unsaturated compounds in water and palladium acetate obviously promoted these transformations. The reported method, overcoming the inactivation of palladium under the equivalent nitrogenous conditions, has the advantages of convenient manipulation, atom-economy, as well as environmental friendliness. The bioactive results showed that butyl 3-(5,6-dimethyl-1H-benzo[d]imidazol-1-yl)propanoate (3c) exhibited excellent inhibitory activity against Bacillus subtilis (MIC = 16 μg/mL) and Bacillus proteus (MIC = 8 μg/mL). Therefore, this process would facilitate the construction of various potential bioactive compounds based on the benzimidazole scaffold under mild conditions.N-Alkylated benzimidazole derivatives have been synthesized via the aza-Michael addition reactions of 1H-benzimidazoles to α,β-unsaturated compounds in water and palladium acetate obviously promoted these transformations. The reported method, overcoming the inactivation of palladium under the equivalent nitrogenous conditions, has the advantages of straightforward manipulation, atom-economy, as well as environmental friendliness.

Synthesis and biological evaluation of Schiff base-linked imidazolyl naphthalimides as novel potential anti-MRSA agents

Co-reporter:Huo-Hui Gong, Kishore Baathulaa, Jing-Song Lv, Gui-Xin Cai and Cheng-He Zhou

MedChemComm 2016 vol. 7(Issue 5) pp:924-931

Publication Date(Web):24 Feb 2016

DOI:10.1039/C5MD00574D

A series of novel Schiff base-linked imidazole naphthalimides were developed and their antimicrobial behavior demonstrated that compound 9i could effectively inhibit the growth of some tested strains, especially for MRSA (MIC = 0.003 μmol mL−1), which was superior to the reference drugs. Bacterial membrane permeabilization, bacterial resistance and time-kill kinetic assays of compound 9i against MRSA manifested that it was able to permeate the cell membrane, rapidly kill the tested strains and stall the development of bacterial resistance. Preliminary research revealed that compound 9i could form a stable complex with calf thymus DNA by intercalation mode. These results suggested that compound 9i could serve as a promising anti-MRSA candidate.

Copper-Catalyzed Inter/Intramolecular N-Alkenylation of Benzimidazoles via Tandem Processes Involving Selectively Mild Iodination of sp3 C–H Bond at α-Position of Ester

Co-reporter:Ting-Ting Lai, Dan Xie, Cheng-He Zhou, and Gui-Xin Cai

The Journal of Organic Chemistry 2016 Volume 81(Issue 19) pp:8806-8815

Publication Date(Web):September 7, 2016

DOI:10.1021/acs.joc.6b01465

Inter/intramolecular approaches to sp2 C–N bond formation of N-alkenyl benzimidazoles have been accomplished in the presence of an iodide anion associated with a copper catalyst. Both intermolecular and intramolecular reactions included tandem processes, in which selective iodination of sp3 C–H bond at the α-position of ester under mild conditions was demonstrated for the first time. Tandem reactions involving sp3 C–H activation via α-iodo ester intermediate under copper catalysis efficiently provided more than 20 novel azole compounds, and free radicals were not involved in this transformation.

Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents

Co-reporter:Xue-Jie Fang, Ponmani Jeyakkumar, Srinivasa Rao Avula, Qian Zhou, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2016 26(11) pp: 2584-2588

Publication Date(Web):1 June 2016

DOI:10.1016/j.bmcl.2016.04.036

A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4 μg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c–DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423.

Coumarin-derived azolyl ethanols: synthesis, antimicrobial evaluation and preliminary action mechanism

Co-reporter:Xin-Mei Peng;Kannekanti Vijaya Kumar;Guri L.V. Damu

Science China Chemistry 2016 Volume 59( Issue 7) pp:878-894

Publication Date(Web):2016 July

DOI:10.1007/s11426-015-0351-0

A series of coumarin-derived azolyl ethanols including imidazolyl, triazolyl, tetrazolyl, benzotriazolyl, thiol-imidazolyl and thiol-triazolyl ones were conveniently synthesized and characterized by IR, 1H NMR, 13C NMR and high-resolution mass spectra (HRMS) spectra. Some of the prepared compounds showed appropriate logPow values and effective antibacterial and antifungal activities. Noticeably, compound 14 with bis-triazolyl ethanol group exhibited low minimal inhibitory concentration (MIC) value of 8 mg/mL against MRSA, which was comparable or even superior to reference drugs Norfloxacin (MIC=8 mg/mL) and Chloramphenicol (MIC=16 mg/mL). It could also effectively inhibit the growth of the tested fungal strains compared to Fluconazole. Further binding studies of coumarin 14 with calf thymus DNA were investigated by UV-Vis absorption and fluorescence spectroscopy. It was found that compound 14 could interact with calf thymus DNA by groove binding to form 14-DNA complex via both hydrogen bonds and van der Waals force, which might be the factor to exert the powerful antimicrobial activity.

Synthesis of novel sulfonamide azoles via C–N cleavage of sulfonamides by azole ring and relational antimicrobial study

Co-reporter:Hui-Zhen Zhang, Ponmani Jeyakkumar, Kannekanti Vijaya Kumar and Cheng-He Zhou

New Journal of Chemistry 2015 vol. 39(Issue 7) pp:5776-5796

Publication Date(Web):19 May 2015

DOI:10.1039/C4NJ01932F

A series of novel sulfonamide azoles were synthesized via C–N cleavage of sulfonamides by an azole ring. This type of reaction could be performed smoothly in DMF and some influential factors including temperature, solvent and reaction time to this reaction were also investigated. The antimicrobial results revealed that sulfonamide 9d bearing a 2-methyl-5-nitroimidazole moiety gave the best anti-P. aeruginosa efficiency in this series and was equivalent to chloromycin (MIC = 16 μg mL−1). The combination of sulfonamide azole 9d with chloromycin, norfloxacin, or fluconazole gave significant synergistic effects. Further research showed that compound 9d could effectively intercalate into calf thymus DNA to form the 9d–DNA complex, which might block DNA replication to exert its powerful antimicrobial activity. The transportation behavior of this compound using human serum albumin (HSA) demonstrated that the electrostatic interactions played major roles in the strong association of compound 9d with HSA.

Design, Synthesis, and Antimicrobial Evaluation of Novel Quinolone Imidazoles and Interactions with MRSA DNA

Co-reporter:Ling Zhang;Kannekanti Vijaya Kumar;Syed Rasheed;Rong-Xia Geng

Chemical Biology & Drug Design 2015 Volume 86( Issue 4) pp:648-655

Publication Date(Web):

DOI:10.1111/cbdd.12532

A novel series of quinolone imidazoles as new type of antimicrobial agents were synthesized. Most compounds exhibited good bioactivities especially against MRSA even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs and gave low cytotoxicity to human cells. The pKa values of these compounds showed appropriate ranges to pharmacokinetic behaviors. The interactions between compound 8b, Cu²⁺ ion, and MRSA DNA revealed that compound 8b could intercalate into DNA through copper ion bridge to form a steady 8b–Cu²⁺–DNA ternary complex which might further block DNA replication to exert the powerful bioactivities. Study of compound 8b with human serum albumin indicated that compound 8b could be effectively stored and carried by human serum albumin.

Correction: Design, synthesis, and antibacterial evaluation of novel azolylthioether quinolones as MRSA DNA intercalators

Co-reporter:Ling Zhang, Kannekanti Vijaya Kumar, Syed Rasheed, Shao-Lin Zhang, Rong-Xia Geng and Cheng-He Zhou

MedChemComm 2015 vol. 6(Issue 7) pp:1405-1406

Publication Date(Web):29 Jun 2015

DOI:10.1039/C5MD90029H

Correction for 'Design, synthesis, and antibacterial evaluation of novel azolylthioether quinolones as MRSA DNA intercalators' by Ling Zhang et al., Med. Chem. Commun., 2015, DOI: 10.1039/c5md00186b.

Design, synthesis, and antibacterial evaluation of novel azolylthioether quinolones as MRSA DNA intercalators

Co-reporter:Ling Zhang, Kannekanti Vijaya Kumar, Syed Rasheed, Shao-Lin Zhang, Rong-Xia Geng and Cheng-He Zhou

MedChemComm 2015 vol. 6(Issue 7) pp:1303-1310

Publication Date(Web):21 May 2015

DOI:10.1039/C5MD00186B

A series of azolylthioetherquinolones was synthesized and characterized by NMR, IR, MS and HRMSspectroscopy. All the newly prepared compounds were screened for their antimicrobial activities. Bioactive assay manifested that most of the azolylthioether quinolones exhibited good antimicrobial activities. Especially, imidazolylthioether quinolone 4e displayed remarkable anti-MRSA and anti-P. aeruginosa efficacies with low MIC values of 0.25 μg mL−1, even superior to reference drugs. They induced bacterial resistance more slowly than clinical drugs. Molecular docking study indicated strong binding interactions of compound 4e with topoisomerase IV–DNA complex, which correlated with the inhibitory effect. The preliminarily interactive investigation of compound 4e with genomic DNA isolated from MRSA revealed that compound 4e could intercalate into MRSA DNA through a copper ion bridge to form a steady 4e–Cu2+–DNA ternary complex which might further block DNA replication to exert the powerful bioactivities.

Synthesis and biological evaluation of a new class of quinazolinone azoles as potential antimicrobial agents and their interactions with calf thymus DNA and human serum albumin

Co-reporter:Li-Ping Peng, Sangaraiah Nagarajan, Syed Rasheed and Cheng-He Zhou

MedChemComm 2015 vol. 6(Issue 1) pp:222-229

Publication Date(Web):08 Oct 2014

DOI:10.1039/C4MD00281D

A series of novel quinazolinone azoles were synthesized and characterized by NMR, IR, MS and HRMS spectra. Bioactive assays showed that some target compounds exhibited significant antimicrobial potency. Especially, nitroimidazole derivative 3a displayed comparable or even superior antibacterial efficacies (MIC = 0.03–0.05 μmol mL−1) in contrast with norfloxacin (MIC = 0.01–0.05 μmol mL−1) and chloromycin (MIC = 0.02–0.10 μmol mL−1). The preliminary interactive investigations of compound 3a with calf thymus DNA by UV-vis spectroscopy revealed that compound 3a could bind to DNA to form compound 3a–DNA complex by an intercalative mode and further block DNA replication to exert powerful antibacterial and antifungal activities. Hydrogen bonds and van der Waals forces played important roles in the association of compound 3a–HSA.

Synthesis of tetrazole compounds as a novel type of potential antimicrobial agents and their synergistic effects with clinical drugs and interactions with calf thymus DNA

Co-reporter:Ling-Ling Dai, Hui-Zhen Zhang, Sangaraiah Nagarajan, Syed Rasheed and Cheng-He Zhou

MedChemComm 2015 vol. 6(Issue 1) pp:147-154

Publication Date(Web):22 Sep 2014

DOI:10.1039/C4MD00266K

A series of tetrazole derivatives were synthesized and characterized by NMR, IR, MS and HRMS spectroscopy. The bioactive assay manifested that most of the target compounds exhibited good antifungal activity, especially compound 6g displayed comparable or even stronger antifungal efficiency in comparison with the reference drug Fluconazole. The combination of tetrazole derivative 6g with antibacterials Chloromycin and Norfloxacin, or antifungal Fluconazole respectively was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive Aspergillus flavus. Further research revealed that compound 6g could effectively intercalate into Calf Thymus DNA to form a 6g–DNA complex which might block DNA replication to exert its good antimicrobial activities.

Novel benzimidazole derived naphthalimide triazoles: synthesis, antimicrobial activity and interactions with calf thymus DNA

Co-reporter:Yun-Lei Luo;Kishore Baathulaa;Vijaya Kumar Kannekanti

Science China Chemistry 2015 Volume 58( Issue 3) pp:483-494

Publication Date(Web):2015 March

DOI:10.1007/s11426-014-5296-3

A novel series of benzimidazole derived naphthalimide triazoles and some corresponding triazoliums have been successfully synthesized and characterized by 1H NMR, 13C NMR, 1H-1H COSY, IR and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by two-fold serial dilution. 2-Chlorobenzyl triazolium 8g and compound 9b with octyl group exhibited the best antibacterial activities among all the tested compounds, especially against S. aureus with inhibitory concentration of 2 μg/mL which was equipotent potency to Norfloxacin (MIC=2 μg/mL) and more active than Chloromycin (MIC=7 μg/mL). Triazoliums 8g and 8f bearing 3-fluorobenzyl moiety displayed the best antifungal activities (MIC=2−19 μg/mL) against all the tested fungal strains without being toxic to PC12 cell line within concentration of 128 μg/mL. Further investigations by fluorescence and UV-Vis spectroscopic methods revealed that the compound 8g could effectively intercalate into calf thymus DNA to form the 8g-DNA complex which could block DNA replication, exerting powerful antimicrobial activities.

Synthesis and biological evaluation of novel d-glucose-derived 1,2,3-triazoles as potential antibacterial and antifungal agents

Co-reporter:Hui-Zhen Zhang;Jin-Jian Wei;Kannekanti Vijaya Kumar

Medicinal Chemistry Research 2015 Volume 24( Issue 1) pp:182-196

Publication Date(Web):2015 January

DOI:10.1007/s00044-014-1123-9

A series of novel d-glucose-derived 1,2,3-triazoles have been synthesized in excellent yields via Cu(I)-catalyzed 1,3-dipolar cycloaddition by using methyl α-d-glucopyranoside as starting material. All the new compounds were confirmed by 1H NMR, 13C NMR, IR, MS, and HRMS spectra, and their antimicrobial activities were screened against Gram-Positive, Gram-Negative bacteria, and fungi. Bioactive assay manifested that some of the synthesized glucose-derived 1,2,3-triazoles exhibited good antibacterial and antifungal activities. Notably, compound 5k gave the most potent efficiency with MIC50 value of 6 µM against Candida albicans, which was nine-fold more active than the reference drug Fluconazole. It also exhibited good antibacterial activity against Escherichia coli with the MIC50 value of 10.8 µM compared to Chloramphenicol while the corresponding hydrochloride 4k revealed remarkable inhibitory against Bacillus subtilis with an MIC50 value of 11 µM.

Novel hybrids of metronidazole and quinolones: Synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin

Co-reporter:Sheng-Feng Cui, Li-Ping Peng, Hui-Zhen Zhang, Syed Rasheed, Kannekanti Vijaya Kumar, Cheng-He Zhou

European Journal of Medicinal Chemistry 2014 Volume 86() pp:318-334

Publication Date(Web):30 October 2014

DOI:10.1016/j.ejmech.2014.08.063

•Synthesis of a novel series of hybrids of metronidazole and quinolones.•Valuable antimicrobial potency and broad spectrum for some prepared hybrids.•No toxicity of metronidazole–quinolones hybrids to A549 and hepatocyte cells.•Competitive interactions of strong active compound with metal ions to HSA.•Experimental results showing stronger binding ability with topo IV than norfloxacin.A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole–quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg2+ ion in compound 7d–HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV–DNA complex.A series of metronidazole–quinolones hybrids were designed and synthesized. Their antimicrobial activities, pKa, cytotoxicity, preliminary antimicrobial mechanism and their transportation by HSA were studied.

Synthesis and biological evaluation of α-triazolyl chalcones as a new type of potential antimicrobial agents and their interaction with calf thymus DNA and human serum albumin

Co-reporter:Ben-Tao Yin, Cong-Yan Yan, Xin-Mei Peng, Shao-Lin Zhang, Syed Rasheed, Rong-Xia Geng, Cheng-He Zhou

European Journal of Medicinal Chemistry 2014 Volume 71() pp:148-159

Publication Date(Web):7 January 2014

DOI:10.1016/j.ejmech.2013.11.003

•Synthesis and valuable antimicrobial potency of α-triazolyl chalcones.•Some prepared compounds were highly sensitive to MRSA.•Intercalation of 9a into DNA revealed to be responsible for antimicrobial activity.•α-Triazolyl chalcone 9a could be effectively stored and carried by HSA.•Some metal ions were found to increase the concentration of free compound 9a.A series of α-triazolyl chalcones were efficiently synthesized. Most of the prepared compounds showed effective antibacterial and antifungal activities. Noticeably, α-triazolyl derivative 9a exhibited low MIC value of 4 μg/mL against MRSA and Micrococcus luteus, which was comparable or even superior to reference drugs. The further research revealed that compound 9a could effectively intercalate into Calf Thymus DNA to form 9a–DNA complex which might block DNA replication to exert their powerful antimicrobial activities. Competitive interactions between 9a and metal ions to Human Serum Albumin (HSA) suggested the participation of Fe3+, K+ and Mg2+ ions in 9a–HSA system could increase the concentration of free 9a, shorten its storage time and half-life in the blood, thus improving its antimicrobial efficacy.A series of α-triazolyl chalcones were synthesized and screened for their antimicrobial activities, further binding behavior with calf thymus DNA and human serum albumin was investigated.

A unique one-pot reaction via CC cleavage from aminomethylene benzimidazoles to access benzimidazolones with wide potentiality

Co-reporter:Hui-Zhen Zhang, Sheng-Feng Cui, Sangaraiah Nagarajan, Syed Rasheed, Gui-Xin Cai, Cheng-He Zhou

Tetrahedron Letters 2014 Volume 55(Issue 30) pp:4105-4109

Publication Date(Web):23 July 2014

DOI:10.1016/j.tetlet.2014.05.113

A unique one-pot reaction via CC cleavage from aminomethylene benzimidazoles with commercial halides to access novel benzimidazolones is reported for the first time. The previously unexploited transformation is able to perform smoothly in the presence of commercial potassium carbonate, while the stronger inorganic bases or organic amines as catalysts are not favorable to the transformation. Significant influential factors including base, temperature, solvent, water content, and molar ratio of substrates to this reaction are investigated, and possibly mechanistic consideration is also discussed. Some synthesized benzimidazolones were evaluated and exhibited better bioactivities against tested strains than clinical drugs chloromycin, norfloxacin, and fluconazole.

Synthesis and bioactive evaluation of a novel series of coumarinazoles

Co-reporter:Guri L.V. Damu, Sheng-Feng Cui, Xin-Mei Peng, Qin-Mei Wen, Gui-Xin Cai, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 15) pp:3605-3608

Publication Date(Web):1 August 2014

DOI:10.1016/j.bmcl.2014.05.029

A series of novel coumarinazoles were designed, synthesized, and characterized by IR, NMR, MS and HRMS spectra. The bioactive assay for the newly prepared compounds against six bacteria and five fungi manifested that most new compounds exhibited good or even stronger antibacterial and antifungal activities in comparison with reference drugs Chloromycin, Norfloxacin and Fluconazole. Bis-azole alcohols 7a and 7d–e showed better anti-Candida utilis activity than mono-azole derivatives 4a and 4d–e at the tested concentrations, and they were more potent than the clinical Fluconazole. While triazole alcohol 7a gave comparable anti-Candida albicans and anti-Candida mycoderma activity to Fluconazole and better anti-MRSA activity than mono-triazole one 4a and clinical Norfloxacin. 1H-Benzoimidazol-2-ylthio coumarin derivatives 4e and 7e gave the strongest anti-Escherichia coli JM109 efficacy. Oxiran-2-ylmethoxy moiety was found to be a beneficial fragment to improve antibacterial and antifungal activity to some extent.Figure optionsDownload full-size imageDownload high-quality image (127 K)Download as PowerPoint slide

1,2,3-Triazole-derived naphthalimides as a novel type of potential antimicrobial agents: Synthesis, antimicrobial activity, interaction with calf thymus DNA and human serum albumin

Co-reporter:Jing-Song Lv, Xin-Mei Peng, Baathulaa Kishore, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 1) pp:308-313

Publication Date(Web):1 January 2014

DOI:10.1016/j.bmcl.2013.11.013

A series of 1,2,3-triazole-derived naphthalimides as a novel type of potential antimicrobial agents were synthesized and characterized by IR, NMR and HRMS spectra. All the new compounds were screened for their antimicrobial activity against four Gram-positive bacteria, four Gram-negative bacteria and three fungi. Bioactive assay manifested that 3,4-dichlorobenzyl compound 9e and its corresponding hydrochloride 11e showed better anti-Escherichia coli activity than Norfloxacin and Chloromycin. Preliminary research revealed that compound 9e could effectively intercalate into calf thymus DNA to form compound 9e–DNA complex which might block DNA replication and thus exert antimicrobial activities. Human serum albumin could effectively store and carry compound 9e by electrostatic interaction.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs

Co-reporter:HuiZhen Zhang;JianMei Lin;Syed Rasheed;ChengHe Zhou

Science China Chemistry 2014 Volume 57( Issue 6) pp:807-822

Publication Date(Web):2014 June

DOI:10.1007/s11426-014-5087-x

A series of new benzimidazole derivatives was synthesized and characterized by IR, 1H NMR, 13C NMR, MS, and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin, Norfloxacin, and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin, Norfloxacin, and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A. flavus. In addition, the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.

Synthesis and bioactive evaluation of novel hybrids of metronidazole and berberine as new type of antimicrobial agents and their transportation behavior by human serum albumin

Co-reporter:Ling Zhang, Juan-Juan Chang, Shao-Lin Zhang, Guri L.V. Damu, Rong-Xia Geng, Cheng-He Zhou

Bioorganic & Medicinal Chemistry 2013 Volume 21(Issue 14) pp:4158-4169

Publication Date(Web):15 July 2013

DOI:10.1016/j.bmc.2013.05.007

A series of novel hybrids of metronidazole and berberine as new type of antimicrobial agents were synthesized and characterized by 1H NMR, 13C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that most of the prepared compounds exhibited effective antibacterial and antifungal activities and some showed comparable or superior potency against Methicillin-resistant Staphylococcus aureus to reference drugs Norfloxacin, Chloromycin and Berberine. The transportation behavior of human serum albumin (HSA) to the highly active compound 5g was evaluated and revealed that the association of imidazole derivative 5g with HSA was spontaneous and the electrostatic interactions played important roles in the transportation of HSA to 5g. The calculated parameters indicated that compound 5g could be effectively stored and carried by HSA.

Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

Co-reporter:Sheng-Feng Cui, Yu Ren, Shao-Lin Zhang, Xin-Mei Peng, Guri L.V. Damu, Rong-Xia Geng, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2013 Volume 23(Issue 11) pp:3267-3272

Publication Date(Web):1 June 2013

DOI:10.1016/j.bmcl.2013.03.118

A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV–vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b–DNA complex which might block DNA replication and thus exert its antimicrobial activities.

Berberine azoles as antimicrobial agents: synthesis, biological evaluation and their interactions with human serum albumin

Co-reporter:Shao-Lin Zhang, Juan-Juan Chang, Guri L. V. Damu, Rong-Xia Geng and Cheng-He Zhou

MedChemComm 2013 vol. 4(Issue 5) pp:839-846

Publication Date(Web):11 Mar 2013

DOI:10.1039/C3MD00032J

A series of berberine azoles was synthesized and characterized by NMR, IR, MS and HRMS spectroscopy. All the newly prepared compounds were screened for their antimicrobial activities. Bioactivity assays manifested that most of the berberine azoles exhibited good antimicrobial activities. Especially compound 7a displayed remarkable anti-Proteus vulgaris and anti-Candida mycoderma efficacies, which were comparable to or even better than for the reference drugs. The binding behavior of compound 7a to human serum albumin (HSA) revealed that hydrophobic interactions and hydrogen bonds play important roles in the association of compound 7a with HSA. Molecular docking experiments showed that compound 7a has moderate affinity to HSA, and the theoretical calculations were in accordance with the experimental results.

A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents

Co-reporter:Guri L. V. Damu;QingPeng Wang;HuiZhen Zhang;YiYi Zhang

Science China Chemistry 2013 Volume 56( Issue 7) pp:952-969

Publication Date(Web):2013 July

DOI:10.1007/s11426-013-4873-1

A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-1,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher efficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed.

Design, synthesis and evaluation of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents

Co-reporter:Yan Wang, Guri L.V. Damu, Jing-Song Lv, Rong-Xia Geng, Da-Cheng Yang, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 17) pp:5363-5366

Publication Date(Web):1 September 2012

DOI:10.1016/j.bmcl.2012.07.064

A series of clinafloxacin triazole hybrids as a new type of antibacterial and antifungal agents were synthesized for the first time and screened for their antimicrobial efficacy against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two fold serial dilution technique. The bioactive assay indicated that most of the target compounds displayed broad antimicrobial spectrum and good antibacterial and antifungal activities with low MIC values ranging from 0.25 to 2 μg/mL against all the tested strains which exhibited comparable or even better efficiency in comparison with the reference drugs Chloramphenicol, Clinafloxacin and Fluconazole, respectively. Notably, some synthesized clinafloxacin triazoles showed stronger efficacy against methicillin-resistant Staphylococcus aureus than their parent Clinafloxacin.

Synthesis and Characterization of Thiophene-derived Amido Bis-nitrogen Mustard and Its Antimicrobial and Anticancer Activities

Co-reporter:Yidan Tang;Jingqing Zhang;Shaolin Zhang;Rongxia Geng;Chenghe Zhou

Chinese Journal of Chemistry 2012 Volume 30( Issue 8) pp:1831-1840

Publication Date(Web):

DOI:10.1002/cjoc.201100668

Abstract

The thiophene-derived amido bis-nitrogen mustard N²,N²,N⁵,N⁵-tetrakis(2-chloroethyl)-3,4-dimethylthiophene-2,5-dicarboxamide was designed and synthesized via five-step reactions from commercially available 2-chloroacetonitrile. This target compound was confirmed by ¹H NMR, ¹³C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X-ray single-crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug-resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line (PC-3), breast carcinoma cell line (MCF-7), colon carcinoma (LoVo) and lung cancer (A549). Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line (PC-3) at a low dose.

Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial and antifungal agents

Co-reporter:QingPeng Wang;JingQing Zhang;Guri L. V. Damu;Kun Wan

Science China Chemistry 2012 Volume 55( Issue 10) pp:2134-2153

Publication Date(Web):2012 October

DOI:10.1007/s11426-012-4602-1

A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1H NMR, 13C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazole-thione and its triazolium derivatives displayed the most potent activities against all the tested strains.

Synthesis of novel fluconazoliums and their evaluation for antibacterial and antifungal activities

Co-reporter:Yi-Yi Zhang, Jia-Li Mi, Cheng-He Zhou, Xiang-Dong Zhou

European Journal of Medicinal Chemistry 2011 Volume 46(Issue 9) pp:4391-4402

Publication Date(Web):September 2011

DOI:10.1016/j.ejmech.2011.07.010

A series of novel fluconazoliums were synthesized and their bioactive evaluation as potential antibacterial and antifungal agents were described. Some target compounds displayed good and broad-spectrum antimicrobial activities with low MIC values ranging from 0.25 to 64 μg/mL against all the tested strains, including three Gram-positive bacteria (Staphylococcus aureus, MRSA and Bacillus subtilis), three Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Bacillus proteus) as well as two fungi (Candida albicans and Aspergillus fumigatus). Among all tested title compounds, the octyl, dichlorobenzyl, naphthyl and naphthalimino derivatives gave comparable or even better antibacterial and antifungal efficiency in comparison with the reference drugs Fluconazole, Chloromycin and Norfloxacin.A series of new fluconazoliums were synthesized and evaluated for their antibacterial and antifungal activities in vitro. Some of them displayed broad antimicrobial spectrum and comparable or even better efficacy in comparison with the reference drugs.Highlights► Synthesis and characterization of a series of novel various fluconazoliums. ► Antibacterial and antifungal evaluation indicating broad antimicrobial spectrum. ► Comparable or superior antibacterial potency to Chloromycin and Norfloxacin for some fluconazoliums. ► Discussion for preliminary possible structure-activity relationships.

Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents

Co-reporter:Yuan Shi, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 3) pp:956-960

Publication Date(Web):1 February 2011

DOI:10.1016/j.bmcl.2010.12.059

A series of new coumarin-based 1,2,4-triazole derivatives were designed, synthesized and evaluated for their antimicrobial activities in vitro against four Gram-positive bacteria (Staphylococcus aureus, MRSA, Bacillus subtilis and Micrococcus luteus), four Gram-negative bacteria (Escherichia coli, Proteus vulgaris, Salmonella typhi and Shigella dysenteriae) as well as three fungi (Candida albicans, Saccharomyces cerevisiae and Aspergillus fumigatus) by two-fold serial dilution technique. The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antibacterial and antifungal efficacy in comparison with reference drugs Enoxacin, Chloromycin and Fluconazole. Coumarin bis-triazole compounds exhibited stronger antibacterial and antifungal efficiency than their corresponding mono-triazole derivatives.A series of new coumarin-based 1,2,4-triazoles were synthesized and some of them displayed comparable or even better antibacterial and antifungal efficacy compared to reference drugs Enoxacin, Chloromycin and Fluconazole.

Synthesis and activities of naphthalimide azoles as a new type of antibacterial and antifungal agents

Co-reporter:Yi-Yi Zhang, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 14) pp:4349-4352

Publication Date(Web):15 July 2011

DOI:10.1016/j.bmcl.2011.05.042

Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16 μg/mL. Notably, some synthesized compounds displayed comparable or even better antibacterial and antifungal activities against some tested strains than the reference drugs Orbifloxacin, Chloromycin and Fluconazole, respectively.Novel naphthalimide-derived azoles were synthesized and evaluated for antimicrobial activities. Most of the tested compounds exhibited good antimicrobial activities with low MIC values ranging from 1 to 16 μg/mL.

Synthesis of novel sulfanilamide-derived 1,2,3-triazoles and their evaluation for antibacterial and antifungal activities

Co-reporter:Xian-Long Wang, Kun Wan, Cheng-He Zhou

European Journal of Medicinal Chemistry 2010 Volume 45(Issue 10) pp:4631-4639

Publication Date(Web):October 2010

DOI:10.1016/j.ejmech.2010.07.031

A series of novel sulfanilamide-derived 1,2,3-triazole compounds were synthesized in excellent yields via 1,3-dipolar cycloaddition and confirmed by MS, IR and NMR spectra as well as elemental analyses. All the compounds were screened in vitro for their antibacterial and antifungal activities. Preliminary results indicated that some target compounds exhibited promising antibacterial potency. Especially, 4-amino-N-((1-dodecyl-1H-1,2,3-triazol-4-yl)methyl) benzenesulfonamide, N-((1-(2,4-dichlorobenzyl)- 1H-1,2,3-triazol-4-yl)methyl)-4-aminobenzenesulfonamide and 4-amino-N-((1-(2,4-difluorobenzyl)- 1H-1,2,3-triazol-4-yl)methyl) benzenesulfonamide were found to be the most potent compounds against all the tested strains except for Candida albicans (ATCC76615) and Candida mycoderma.A series of novel sulfanilamide-derived 1,2,3-triazoles were synthesized and evaluated for their antibacterial and antifungal activities in vitro.

Synthesis, antibacterial and antifungal activities of some carbazole derivatives

Co-reporter:Fei-Fei Zhang, Lin-Ling Gan, Cheng-He Zhou

Bioorganic & Medicinal Chemistry Letters 2010 Volume 20(Issue 6) pp:1881-1884

Publication Date(Web):15 March 2010

DOI:10.1016/j.bmcl.2010.01.159

A series of N-substituted carbazole derivatives were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacillus proteus, Candida albicans and Aspergillus fumigatus by two fold serial dilution technique. Some of the synthesized compounds displayed comparable or even better antibacterial and antifungal activities than reference drugs fluconazole, chloramphenicol and norfloxacin against tested strains.A series of carbazole derivatives were synthesized and evaluated for antibacterial and antifungal activities.

Synthesis, Antibacterial and Antifungal Activities of Novel 1,2,4-Triazolium Derivatives

Co-reporter:Yan Luo;Yi-Hui Lu;Lin-Ling Gan;Jun Wu;Rong-Xia Geng;Yi-Yi Zhang

Archiv der Pharmazie 2009 Volume 342( Issue 7) pp:386-393

Publication Date(Web):

DOI:10.1002/ardp.200800221

Abstract

A series of novel 1,2,4-triazolium derivatives was synthesized starting from commercially available 1H-1,2,4-triazole, 2,4-dichlorobenzyl chloride, or 2,4-difluorobenzyl bromide. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Bacillus proteus, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans ATCC 76615, and Aspergillus fumigatus. All structures of the new compounds were confirmed by NMR, IR, and MS spectra, and elemental analyses. The antimicrobial tests showed that most of synthesized triazolium derivatives exhibit significant antibacterial and antifungal activities in vitro. 1-(2,4-Difluorobenzyl)-4-dodecyl-1H-1,2,4-triazol-4-ium bromide and 1-(2,4-Dichlorobenzyl)-4-dodecyl-1H-1,2,4- triazol-4-ium bromide were the most potent compounds against all tested strains with the MIC values ranging from 1.05 to 8.38 μM. They exhibited much stronger activities than the standard drugs chloramphenicol and fluconazole which are in clinical use. The results also showed that the antimicrobial activities of triazolium derivatives depend upon the type of substituent, the length of the alkyl chain, and the number of triazolium rings.

Review on supermolecules as chemical drugs

Co-reporter:ChengHe Zhou;LinLing Gan;YiYi Zhang;FeiFei Zhang

Science China Chemistry 2009 Volume 52( Issue 4) pp:415-458

Publication Date(Web):2009 April

DOI:10.1007/s11426-009-0103-2

Supramolecular medicinal chemistry field has been a quite rapidly developing, increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceutical sciences, and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through non-covalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs, i.e. supramolecular chemical drugs or supramolecular drugs, which might have the excellences of lower cost, shorter period, higher potential as clinical drugs for their successful research and development, may possess higher bioavailability, better biocompatibility and drug-targeting, fewer multidrug-resistances, lower toxicity, less adverse effect, and better curative effects as well as safety, and therefore exhibit wide potential application. These overwhelming advantages have drawn enormous special attention. This paper gives the definition of supramolecular drugs, proposes the concept of supramolecular chemical drugs, and systematically reviews the recent advances in the research and development of supermolecules, including organic and inorganic complex ones as chemical drugs in the area of antitumor, anti-inflammatory, analgesic, antimalarial, antibacterial, antifungal, antivirus, anti-epileptic, cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented.