Tao Zhou

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Organization: Zhejiang Gongshang University

Department: School of Food Science and Biotechnology

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TOPICS

Inorganic Chemistry

Porphyrin

Organic Chemistry

Peptide Synthesis

Chemicals
References

Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy

Co-reporter:Sinan Battah, Robert C. Hider, Alexander J. MacRobert, Paul S. Dobbin, and Tao Zhou

Journal of Medicinal Chemistry April 27, 2017 Volume 60(Issue 8) pp:3498-3498

Publication Date(Web):March 31, 2017

DOI:10.1021/acs.jmedchem.7b00346

Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA–PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA–HPOs investigated. This study demonstrates that ALA–HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.

Carboxymethylated degraded polysaccharides from Enteromorpha prolifera: Preparation and in vitro antioxidant activity

Co-reporter:Mei-Jia Shi, Xiaoyi Wei, Jie Xu, Bing-Jie Chen, De-Yin Zhao, Shuai Cui, Tao Zhou

Food Chemistry 2017 Volume 215() pp:76-83

Publication Date(Web):15 January 2017

DOI:10.1016/j.foodchem.2016.07.151

•The polysaccharide from E. prolifera was degraded effectively by H2O2 and Vitamin C.•Degraded polysaccharide was carboxymethylated to improve its antioxidant activity.•Conditions for carboxymethylation were optimized by Response Surface Methodology.•The antioxidant activity of carboxymethylated extract was greatly enhanced.In order to improve the bioactivities of the polysaccharide from Enteromorpha prolifera (PE), crude PE (Mw 1400 kDa) was degraded to low molecular weight polysaccharide (44 kDa) in the presence of hydrogen peroxide/ascorbic acid, followed by carboxymethylation. The reaction conditions for carboxymethylation of degraded polysaccharide (DPE) were optimized by Response Surface Methodology. The carboxymethyled degraded polysaccharide (CDPE) obtained under optimized conditions, with a degree of carboxymethylation of 0.849, was characterized by FT-IR and 13C NMR. The molecular weight of CDPE was measured to be 53.7 kDa. CDPE was evaluated for its antioxidant activity by determining the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals, and by determining the ferric reducing power. The antioxidant activity of CDPE was found to be greatly improved in comparison with degraded polysaccharide (DPE) and crude polysaccharide from Enteromorpha prolifera (PE).

Preparation, antioxidant and antimicrobial evaluation of hydroxamated degraded polysaccharides from Enteromorpha prolifera

Co-reporter:Le-Le Shao, Jie Xu, Mei-Jia Shi, Xiao-Ling Wang, Yin-Ting Li, Li-Min Kong, Robert C Hider, Tao Zhou

Food Chemistry 2017 Volume 237(Volume 237) pp:

Publication Date(Web):15 December 2017

DOI:10.1016/j.foodchem.2017.05.119

•Hydroxamated derivative of degraded polysaccharides from E. prolifera was prepared.•The antioxidant activity of the hydroxamated polysaccharide was greatly improved.•Both hydroxamated and carboxylmethylated polysaccharide possess antibacterial activity.In order to improve the antioxidant and antimicrobial abilities, hydroxamated degraded polysaccharides from Enteromorpha prolifera (HCDPE) were prepared from the corresponding carboxymethylated degraded polysaccharides (CDPE). HCDPE was characterized by FT-IR. The weight-average molecular weight of HCDPE was determined as 55.4 kDa. The in vitro antioxidant activity of HCDPE was evaluated by determining the radical (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals) scavenging abilities and total antioxidant activity. It was found that DPPH radical scavenging ability and total antioxidant activity of HCDPE were significantly improved compared to those of CDPE. The inhibitory effects of polysaccharides against the five bacterial strains (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella spp.) were also evaluated by bacterial inhibition zone and minimum inhibitory concentration (MIC) assays. The results indicated that CDPE and HCDPE possess marked antimicrobial ability, while such an effect was not observed for the crude polysaccharides (PE) and the degraded polysaccharides (DPE).

A Novel Inhibitor Against Mushroom Tyrosinase with a Double Action Mode and Its Application in Controlling the Browning of Potato

Co-reporter:Kai Chen;De-Yin Zhao;Yu-Lin Chen;Xiao-Yi Wei

Food and Bioprocess Technology 2017 Volume 10( Issue 12) pp:2146-2155

Publication Date(Web):26 August 2017

DOI:10.1007/s11947-017-1976-2

In order to search for a new method for the anti-browning of food products, a novel hydroxypyridinone (HPO) derivative with a formyl group was evaluated for its anti-tyrosinase property. This compound was found to exhibit potent tyrosinase inhibition on the monophenolase activity of mushroom tyrosinase with an IC50 value of 1.33 μM, indicating that this HPO derivative was 12-fold stronger than kojic acid (IC50 15.89 μM). This molecule can inhibit tyrosinase via two action modes, namely copper reduction and chelation, and the formation of a Schiff’s base with the amino group at the active site of the enzyme. A synergistic effect of these two action modes to enhance the inhibitory activity was observed. This compound was also investigated for the inhibitory effect on diphenolase activity of mushroom; the inhibitory mechanism was found to be reversible and of competitive-uncompetitive mixed-type inhibition. This hydroxypyridinone was demonstrated to effectively control the browning of vegetable products.

Design and synthesis of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates for photodynamic therapy: enhancement of protoporphyrin IX production and photo-toxicity in tumor cells

Co-reporter:Tao Zhou, Le-Le Shao, Sinan Battah, Chun-Feng Zhu, Robert C. Hider, Brandon J. Reeder, Asma Jabeen, Alexander J. MacRobert, Gerui Ren and Xinle Liang

MedChemComm 2016 vol. 7(Issue 6) pp:1190-1196

Publication Date(Web):15 Apr 2016

DOI:10.1039/C6MD00040A

5-Aminolaevulinic acid (ALA) and its derivatives have been widely used in photodynamic therapy (PDT) as precursors of the photosensitizer, protoporphyrin IX (PpIX) in dermatology and urology. However, ALA-PDT is limited by the low bioavailability of ALA due to the fact that ALA is poorly absorbed by cells by virtue of its zwitterionic nature at physiological pH. In order to improve the therapeutic effect and induce higher levels of PpIX, a series of ALA prodrugs were synthesized by the conjugation of ALA to 3-hydroxypyridin-4-one (HPO) iron chelator using an amino acid linkage via amide bonds. Pharmacokinetic studies indicated that one ALA–HPO conjugate significantly enhanced PpIX production in a range of tumor cell lines over ALA alone or the co-administration of ALA and CP94 (1,2-diethyl-3-hydroxypyridin-4-one). The intracellular porphyrin fluorescence levels showed good correlation with cellular photo-toxicity following light exposure, suggesting the potential application of the ALA–HPO conjugates in photodynamic therapy.

Enhanced in Vitro Antioxidant Activity of Polysaccharides From Enteromorpha Prolifera by Enzymatic Degradation

Co-reporter:Jie Xu;Li-Li Xu;Qin-Wei Zhou;Shu-Xian Hao;Hu-Jun Xie

Journal of Food Biochemistry 2016 Volume 40( Issue 3) pp:275-283

Publication Date(Web):

DOI:10.1111/jfbc.12218

Abstract

In order to improve the antioxidant activity of polysaccharide derived from Enteromorpha prolifera (PEP), PEP was hydrolyzed to relatively low molecular weight polysaccharides in the presence of either pectinase or gluco-amylase. Response surface methodology was employed to optimize the hydrolysis conditions based on the polysaccharide degradation rate. Optimum hydrolysis for pectinase was found to be: enzyme concentration 9.36 U/mL, reaction temperature 56C and pH 4.45; for gluco-amylase, the optimum conditions were: enzyme concentration 14.20 U/mL, reaction temperature 49C and pH 4.48. The enzymatic hydrolysates of polysaccharide obtained under optimal conditions were evaluated for their antioxidant activities by determining their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals. The results indicate that the enzymatic hydrolysates of polysaccharide exhibited stronger free radical scavenging ability than nondegraded polysaccharide, while pectinase hydrolyzed polysaccharide was found to possess superior radical scavenging ability to that of gluco-amylase hydrolyzed polysaccharide.

Practical Applications

In order to fully utilize polysaccharide resources, an effective method to improve the antioxidant activity of Enteromorpha prolifera was established by enzymatic degradation. The hydrolysates obtained by this method may be used as ingredients of functional foods due to their antioxidant activity.

Antioxidant Activity of Enzymatic Hydrolysate Derived From Hairtail Surimi Wash Water Using an Immobilized ChymotrypsinTrypsin Column Reactor

Co-reporter:Qin-Wei Zhou;Hao-Chen Ding;Dong-Fang Li;Yan-Ping Zhang;Zhi-Yuan Dai

Journal of Food Biochemistry 2016 Volume 40( Issue 1) pp:39-46

Publication Date(Web):

DOI:10.1111/jfbc.12185

Abstract

In this study, a column reactor filled with immobilized chymotrypsin–trypsin (I-CT) was used to prepare antioxidant peptides from hairtail surimi wash water. At the optimum reaction temperature (30C), when residence time is 5 min (flow rate is 3 mL/min), the conversion rate of the I-CT column enzymatic reactor could be maintained above 60%. The half-life of the column reactor was in excess of 6 h. At 30C, when residence time is 15 min (flow rate is 1 mL/min), the antioxidant capacity of the resulting enzymatic hydrolysate was the highest (1.59 mmol/L FeSO₄ equivalent) and the product conversion rate was 67.0%. Tricine–sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis showed that the main ingredients of enzymatic hydrolysate were low-molecular-weight peptides (<4 kDa).

Practical Applications

In order to fully utilized protein resources, it is necessary to develop an effective approach to recover protein in the surimi wash water. To this end, a practical method by using a column reactor filled with immobilized chymotrypsin–trypsin developed in our laboratory was established. The hydrolysates obtained by this method may be used as ingredients of functional foods due to their antioxidant activity.

Novel Multifunctional Hydroxypyridinone Derivatives as Potential Shrimp Preservatives

Co-reporter:Xiao-Yan Dai;Ming-Xia Zhang;Xiao-Yi Wei;Robert C Hider

Food and Bioprocess Technology 2016 Volume 9( Issue 7) pp:1079-1088

Publication Date(Web):2016 July

DOI:10.1007/s11947-016-1694-1

In order to develop a new efficient method for the prolongation of shrimp shelf life, two novel hydroxypyridinone derivatives ((S)-2-amino-N-((S)-1-(((5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl)amino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide (2) and (S)-(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl 2-(benzyloxycarbonyl)-3- phenylpropanoate (3)) possessing strong tyrosinase inhibitory activity were investigated to explore their potential as shrimp preservatives. Their antimicrobial activities were evaluated by a disk diffusion method. Inhibition zone assays indicated that both 2 and 3 possess a stronger inhibitory effect than kojic acid. The minimum inhibition concentrations (MICs) of compound 3 against Bacillus subtilis, Staphylococcous aureus, Escherichia coli, Salmonella spp., and Pseudomonas aeruginosa were determined to be 32, 32, 32, 8, and 16 μg/mL. Both 2 and 3 were also found to possess antioxidant activity. The IC50 values of 2 and 3 for scavenging DPPH radical were measured to be 2.93 and 2.37 mg/mL, respectively. At 4 mg/mL, 2 and 3 were determined to have total antioxidant capacity of 2.43 and 2.72 U/mL, respectively. Compound 3 was further investigated for efficacy in shrimp preservation by sensory evaluation, determination of total volatile basic nitrogen (TVB-N), pH, and total bacterial count. The treatment with 3 was found to extend the shelf life of Penaeus vannamei Boone to 10 days at 4 °C, while the shelf life of shrimp treated with 4-hexylresorcinol, kojic acid, and the control group was 9, 6, and 4 days, respectively. Compound 3 could find application in the food industry, as a shrimp preservative, due to its protective properties.

Edible Antimicrobial Coating Incorporating a Polymeric Iron Chelator and Its Application in the Preservation of Surimi Product

Co-reporter:Bing-Jie Chen;Ying-Jun Zhou;Xiao-Yi Wei;Hu-Jun Xie

Food and Bioprocess Technology 2016 Volume 9( Issue 6) pp:1031-1039

Publication Date(Web):2016 June

DOI:10.1007/s11947-016-1693-2

To explore a novel efficient method in food preservation, edible zein coating which incorporates a polymeric chelator was developed and its preservative effect on commercially manufactured fish balls was investigated. The quality indicators of the fish ball during the storage, including sensory quality, total bacterial count, total basic volatile nitrogen (TVB-N) content, thiobarbituric acid reactive substances (TBARS), and pH value were determined. It has been demonstrated that a zein film containing a polymeric chelator significantly (P < 0.05) improves the sensory properties, retards the growth of spoilage bacteria, and decreases TVB-N and TBARS values. The increase of the microbial load of fish balls coated with antimicrobial zein during a 16-day refrigeration storage period was less than 1 log cfu/g, while the microbial load increased to about 5 log cfu/g for the control group lacking the coating treatment. Although statistically significant differences in the pH values were not observed between coated and uncoated fish balls (P > 0.05), fish balls coated with antimicrobial zein maintained a relatively stable state during storage. Zein coating which incorporates a polymeric chelator extends fish ball shelf life to 19 days at 4 °C, being more efficient than zein coating lacking a polymeric chelator (13 days). Clearly, polymeric chelator-incorporated zein film could find application in the preservation of surimi products by preventing the growth of bacteria and oxidation of fat during storage.

Design and synthesis of novel hydroxypyridinone derivatives as potential tyrosinase inhibitors

Co-reporter:De-Yin Zhao, Ming-Xia Zhang, Xiao-Wu Dong, Yong-Zhou Hu, Xiao-Yan Dai, Xiaoyi Wei, Robert C. Hider, Jin-Chao Zhang, Tao Zhou

Bioorganic & Medicinal Chemistry Letters 2016 26(13) pp: 3103-3108

Publication Date(Web):1 July 2016

DOI:10.1016/j.bmcl.2016.05.006

Two groups of novel hydroxypyridinone derivatives 6(a–e) and 12(a–c), were designed as potential tyrosinase inhibitors, and synthesized using kojic acid as a starting material. The tyrosinase inhibitory activity of these two groups was demonstrated to be potent, especially compounds 6e and 12a, whose IC50 values for monophenolase activity were 1.95 μM and 2.79 μM, respectively. Both of these values are lower than that of kojic acid (IC50 = 12.50 μM). Compounds 6e and 12a were investigated for the inhibitory effect on diphenolase activity. The results showed that the inhibitory mechanism of these two compounds was reversible and that the inhibitory type was a competitive-uncompetitive mixed-type. The values of IC50 of 6e and 12a on the diphenolase activity of tyrosinase were determined to be 8.97 μM and 26.20 μM, respectively. The inhibitory constants (KI and KIS) of 6e were determined as 17.17 μM and 22.09 μM, respectively; and the KI and KIS values of 12a were 34.41 μM and 79.02 μM, respectively. Compound 6e showed a greater ability to reduce copper and a stronger copper chelating ability than kojic acid.

Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: Design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains

Co-reporter:Ying-Jun Zhou, Mu-Song Liu, Al Rugaie Osamah, Xiao-Le Kong, Selwa Alsam, Sinan Battah, Yuan-Yuan Xie, Robert C. Hider, Tao Zhou

European Journal of Medicinal Chemistry 2015 Volume 94() pp:8-21

Publication Date(Web):13 April 2015

DOI:10.1016/j.ejmech.2015.02.050

•A series of novel hexadentate 3-hydroxypyridin-4-one ligands have been synthesized.•These chelators possess a high affinity for iron(III).•Some exhibit a moderate inhibitory effect on MRSA (MIC 384 μg/mL) and Pseudomonas sp. (MIC 256 μg/mL).A range of hexadentate 3-hydroxypyridin-4-ones have been synthesized. These compounds were found to possess a high affinity for iron(III), with logK1 values of about 34 and pFe values over 30. Antimicrobial assays indicated that they can inhibit the growth of three clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) and three clinical isolates of Pseudomonas, suggesting that hexadentate 3-hydroxypyridin-4-ones have potential application in the treatment of wound infections.A range of hexadentate 3-hydroxypyridin-4-ones with a high iron(III) affinity have been synthesized. They were found to exhibit a significant inhibitory effect on clinical isolates of MRSA and Pseudomonas strains.

Theoretically exploring the key role of the Lys412 residue in the conversion of N2O to N2 by nitrous oxide reductase from Achromobacter cycloclastes

Co-reporter:Hujun Xie, Chengcheng Liu, Xuelin Chen, Qunfang Lei, Wenjun Fang and Tao Zhou

New Journal of Chemistry 2015 vol. 39(Issue 10) pp:8093-8099

Publication Date(Web):11 Aug 2015

DOI:10.1039/C5NJ01339A

Density functional theory (DFT) calculations have been performed to investigate the N2O reduction reaction mechanism catalyzed by the μ4-sulfide-bridged tetranuclear CuZ cluster of nitrous oxide reductase from Achromobacter cycloclastes. Our calculations showed that the active site CuZ cluster can provide strong back-donation to N2O, facilitating N–O bond cleavage. In addition, the Lys412 residue near the CuI/CuIV edge of the CuZ cluster is considered as a suitable proton donor and plays a key role in the reduction reaction. The predicted activation barrier of N–O bond dissociation for the energetically favorable pathway with the terminal nitrogen atom of N2O coordinated to the CuI center is only 14.6 kcal mol−1 in the protein environment. The barrier is significantly lower than the barrier in the absence of the Lys412 residue and CuZ cluster. The relatively low barrier is ascribed to the N–O bond cleavage coupled with the oxygen-atom protonation of the coordinated N2O. Present calculations provide significant insights into the mode of substrate coordination, activation, reduction and catalysis.

Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents

Co-reporter:Chun-Feng Zhu, Sinan Battah, Xiaole Kong, Brandon J. Reeder, Robert C. Hider, Tao Zhou

Bioorganic & Medicinal Chemistry Letters 2015 Volume 25(Issue 3) pp:558-561

Publication Date(Web):1 February 2015

DOI:10.1016/j.bmcl.2014.12.018

5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA–HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA–HPO conjugates in photodynamic therapy.

Design, Synthesis, and Antimicrobial Evaluation of Hexadentate Hydroxypyridinones with High Iron(III) Affinity

Co-reporter:Ming-Xia Zhang;Chun-Feng Zhu;Ying-Jun Zhou;Xiao-Le Kong;Robert C Hider

Chemical Biology & Drug Design 2014 Volume 84( Issue 6) pp:659-668

Publication Date(Web):

DOI:10.1111/cbdd.12358

A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO–iron complexes (logK₁) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 μg/mL, respectively. These results indicate that hexadentate 3-hydroxypyridin-4-ones have potential application as antimicrobial agents, especially in the treatment of wound infection.

Design and Synthesis of Hydroxypyridinone-l-phenylalanine Conjugates as Potential Tyrosinase Inhibitors

Co-reporter:Dong-Fang Li, Pan-Pan Hu, Mu-Song Liu, Xiao-Le Kong, Jin-Chao Zhang, Robert C. Hider, and Tao Zhou

Journal of Agricultural and Food Chemistry 2013 Volume 61(Issue 27) pp:6597-6603

Publication Date(Web):June 13, 2013

DOI:10.1021/jf401585f

A range of hydroxypyridinone-l-phenylalanine conjugates were synthesized starting from kojic acid. Their tyrosinase activity was determined, and it was found that one of the compounds ((S)-(5-(benzyloxy)-1-octyl-4-oxo-1,4-dihydropyridin-2-yl)methyl 2-amino-3-phenylpropanoate, 5e) showed potent inhibitory effect against mushroom tyrosinase, the IC50 values for monophenolase and diphenolase activities being 12.6 and 4.0 μM, respectively. It was also demonstrated that these conjugates are mixed-type inhibitors, suggesting they could bind to both the free enzyme and the enzyme–substrate complexes. MTT assay indicated that 5e was nontoxic to three cell lines. This compound may find applications in food preservation and cosmetics.

Covalent Immobilization of Mixed Proteases, Trypsin and Chymotrypsin, onto Modified Polyvinyl Chloride Microspheres

Co-reporter:Dong-Fang Li, Hao-Chen Ding, and Tao Zhou

Journal of Agricultural and Food Chemistry 2013 Volume 61(Issue 44) pp:10447-10453

Publication Date(Web):October 15, 2013

DOI:10.1021/jf403476p

A commercially available trypsin–chymotrypsin mixture was covalently immobilized onto modified polyvinyl chloride (PVC) microspheres, which were activated by the subsequent treatment of PVC microspheres with ethylenediamine and glutaraldehyde. The immobilized mixed protease was characterized by FT-IR and SEM analyses. Immobilization conditions were optimized by Box–Behnken design and the response surface method. The activity of the immobilized mixed protease prepared under optimal conditions (pH 6.6, 23 °C, 2 h) reached 1341 U/g. Compared with the free form, the immobilized enzyme possesses a slightly higher optimal pH value and a wider pH-activity profile, superior thermal stability, and a higher Km value. Reusability of the immobilized mixed protease indicated that >70% of the original activity was retained after having been recycled six times.

Design, synthesis and biological evaluation of peptide derivatives of l-dopa as anti-parkinsonian agents

Co-reporter:Tao Zhou, Robert C. Hider, Peter Jenner, Bruce Campbell, Christopher J. Hobbs, Sarah Rose, Mark Jairaj, Kayhan A. Tayarani-Binazir, Alexander Syme

Bioorganic & Medicinal Chemistry Letters 2013 23(19) pp: 5279-5282

Publication Date(Web):

DOI:10.1016/j.bmcl.2013.08.007

Synthesis, iron(III)-binding affinity and in vitro evaluation of 3-hydroxypyridin-4-one hexadentate ligands as potential antimicrobial agents

Co-reporter:Bo Xu, Xiao-Le Kong, Tao Zhou, Di-Hong Qiu, Yu-Lin Chen, Mu-Song Liu, Rong-Hua Yang, Robert C. Hider

Bioorganic & Medicinal Chemistry Letters 2011 Volume 21(Issue 21) pp:6376-6380

Publication Date(Web):1 November 2011

DOI:10.1016/j.bmcl.2011.08.097

Iron is a critical element for the survival of bacteria. We have designed and synthesized two novel 3-hydroxypyridin-4-one hexadentate ligands with high affinity for iron(III), which disrupt bacterial iron absorption. Biological studies demonstrate that these two chelators have significant inhibitory effect against both Gram-positive and Gram-negative bacteria, and therefore have potential as antimicrobial agents.Iron is a critical element for the survival of bacteria. We have designed and synthesized two novel 3-hydroxypyridin-4-one hexadentate ligands with high affinity for iron(III), and thus disrupt bacterial iron absorption. Biological studies demonstrate that these two chelators have significant inhibitory effect against both Gram-positive and Gram-negative bacteria, and therefore have potential as antimicrobial agents.