Quanyi Zhao

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Organization: Lanzhou University

Department: School of Pharmacy

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Chemicals
References

Syntheses, toxicities and anti-inflammation of H2S-donors based on non-steroidal anti-inflammatory drugs

Co-reporter:Meng Li, Jili Li, Taofeng Zhang, Quanyi Zhao, Jie Cheng, Bin Liu, Zhen Wang, Libo Zhao, Chenwei Wang

European Journal of Medicinal Chemistry 2017 Volume 138(Volume 138) pp:

Publication Date(Web):29 September 2017

DOI:10.1016/j.ejmech.2017.06.012

•Firstly evaluate the toxicity of H2S-donors based on NSAIDs.•Investigate the effects of H2S-donors on levels of inflammatroy factors.•Explore the synergistic effect of H2S and NSAIDs.Three series of H2S donors based on NSAIDs were synthesized and characterized by 1H-NMR, IR and ESI-HRMS. The H2S-release abilities of all compounds were evaluated in the presence of TECP or cysteine. The results show all compounds were fast H2S-releasers, and their half-lives were in range of 0–20 min. Under the same condition, H2S released from compound 9 was more than any other compounds. In cytotoxicity aspect, all compounds but 1 and 2 displayed much lower toxicities to both LO2 and HepG2 cell lines, and the IC50 values of most compounds were over 800 μM. Compounds 1 and 2 had a stronger anti-proliferative activity to both cell lines, but they displayed lower toxicities to LO2 than to HepG2. Based on the cytotoxicity, the developmental toxicities of the compounds were assessed using zebrafish embryos. The results show all tested compounds 2, 9 and 15 had effects on the mortality, hatching rate and spontaneous movements of zebrafish embryos, and caused embryos teratogenesis; and the compounds had dose-dependent toxicities to both embryonic and larval zebrafish. In addition, all compounds had a better anti-inflammatory activity. In the test of anti-inflammatory activities, the tested compounds all reduced the levels of intracellular nitrite and pro-inflammatory cytokines (TNF-α, COX-2), increased the levels of anti-inflammatory cytokines (IL-10, HO-1). All these suggest these H2S donors based on NSAIDs have a potential to be a candidate medicine.Three series of CORMs H2S-donors based on NSAIDs were evaluated from toxicities and anti-inflammatory activities, and the synergistic effect of H2S and NSAIDs was preliminary explored.Download high-res image (253KB)Download full-size image

Syntheses, properties and bio-activities of water-soluble CO-releasing molecule based on manganese

Co-reporter:Taofeng Zhang;Meng Li;Yaguo Gong;Na Xi

JBIC Journal of Biological Inorganic Chemistry 2016 Volume 21( Issue 7) pp:807-824

Publication Date(Web):2016 October

DOI:10.1007/s00775-016-1379-2

A series of water-soluble CO-releasing molecules, [Mn(CO)3NH2CHRCO2]2 (1–3), [M(CO)3Br[(Py–C = N)(Gly)nCO2] (M = Mn, Re, 4–7), Mn(CO)4[S2CNCmHnCO2] (8–12), were synthesized and characterized by 1H NMR, IR and ESI-HRMS. The stability of all the complexes in solution was evaluated by means of UV, IR and 1H NMR. Among all the complexes, complex 4 and complex 8 were stable in H2O, acidic aqueous solution and basic media; complex 1 was stable in acidic aqueous solution and weak basic media (pH < 9.4). The assays showed that each complex has CO-release ability; excess sodium dithionite can enhance CO release. Among them, complexes 8–12 were fast CO-releasers. In the test of the cell proliferation, all the complexes showed anti-proliferative activities for HeLa and HepG2. In particular, complex 8 displayed a 3.5-fold anti-proliferative activity on HeLa cells (IC50 23.13 μM) and fivefold on HepG2 cells (34.00 μM) compared with 5-FU. What is more, the complexes distinctly influenced cell cycle and promoted cell apoptosis; complex 1 arrested HeLa cells in S phase, whereas complex 4 and complex 8 arrested in G2/M phase; all the complexes induced HeLa cells “Early apoptosis”. In addition, all complexes 1, 4 and 8 decreased intracellular nitrite levels, and complex 8 was stronger than both of the others. All these data demonstrate that complex 8 has potential to be a drug candidate.Three different categories of water-soluble CORMs 1–12 were synthesized, and their stability were evaluated. The biological activities were preliminarily evaluated. This includes anti-proliferation and anti-inflammatory properties.Open image in new window

Syntheses, Cytotoxicity and Properties of CO Releasing Molecules Containing Acetyl Salicylamide-3-pyridine

Co-reporter:Huapeng Liu;Yaguo Gong;Taofeng Zhang;Na Li;Yonglin Chen;Bin Liu;Yawen Zheng

Chinese Journal of Chemistry 2015 Volume 33( Issue 7) pp:739-748

Publication Date(Web):

DOI:10.1002/cjoc.201400824

Abstract

A series of CO-releasing molecules [M(CO)₅L] (M=Cr, W, Mo, L=acetyl salicylamide 3-pyridine, 1–3; L=N,N-dimethyl-4-pyridine, 4–6; L=nicotinamide, 7–9; L=4-CHO-pyridine, 10–12) were synthesized. And in this paper, we have investigated mainly cytotoxicity and properties of the CO-releasing molecules containing acetyl salicyamide-3-pyridine, namely complexes 1–3. The stability of complexes 1 and 2 was evaluated by means of UV-Vis spectroscopy and ¹H NMR spectra. The results indicate complexes 1 and 2 were stable in methanol and acidic aqueous solution, but unstable and decayed in basic media (pH 10.0). Among all the complexes, complex 2 was the slowest CO-releaser, and its half-life was 73.8 min. Complex 9 containing nicotinamide was the fastest CO-releaser with half-life only 6.5 min. In addition, cytotoxic effects of all the complexes on the proliferation of fibroblast line were assayed by MTT. Among all the complexes, the IC₅₀ of complex 1 was 6 µmol/L, revealing complex 1 possessed stronger antiproliferative activity than the control. Analysis by Flow cytometry revealed that complex 1 arrested Hela cells in S phase while complexes 2 and 8 arrested in G2/M phase. Cell apoptosis caused by the complexes mainly occurred in "Late apoptosis".

Synthesis, toxicities and cell proliferation inhibition of CO-releasing molecules containing cobalt

Co-reporter:Yaguo Gong;Taofeng Zhang;Huapeng Liu;Yawen Zheng;Na Li

Transition Metal Chemistry 2015 Volume 40( Issue 4) pp:413-426

Publication Date(Web):2015 May

DOI:10.1007/s11243-015-9931-4

A series of carbon monoxide-releasing molecules (CO-RMs) based on µ2-alkyne dicobalt(0)hexacarbonyl complex esters, Co2(CO)6HCC–CH2OCOR (R = 2-acetyloxybenzoic acid 1; R = 2-hydroxy-benzoic acid 2; R = 3-phenyl-2-propenoic acid 3; R = ibuprofen 4; R = naproxen 5; R = glycyrrhetinic acid 6; R = glycyrrhizic acid 7), were synthesized and characterized by spectroscopic methods. In addition, the crystal structures of complexes 2 and 6 were determined by X-ray diffraction. Cytotoxic effects of all the complexes were assayed by MTT analysis, and their IC50 values were determined as 36–125 µM. Toxicity tests on mice by the oral acute toxic class method gave LD50 values for complexes 1 and 5 in the range of 2500–5000 mg kg−1 and for complex 6 over 5000 mg kg−1. The alkyne substituents significantly affect the rate of CO release and cytotoxicity. The apoptotic effects on HeLa cells were consistent with their cytotoxicities. The cell apoptosis rates were dependent on complex doses, and cell apoptosis mainly occurred by “late apoptosis.” In addition, the complexes also blocked the cell cycle at the G2/M phase and led to the loss of the mitochondrial membrane potential.

Syntheses and evaluation of drug-like properties of CO-releasing molecules containing ruthenium and group 6 metal

Co-reporter:Pengpeng Wang, Huapeng Liu, Quanyi Zhao, Yonglin Chen, Bin Liu, Baoping Zhang, Qian Zheng

European Journal of Medicinal Chemistry 2014 Volume 74() pp:199-215

Publication Date(Web):3 March 2014

DOI:10.1016/j.ejmech.2013.12.041

•Carbon monoxide (CO) is a recently recognized biological signaling molecule.•We evaluate the drug-like properties of some CO-releasing molecules (CORMs).•We investigate their cytotoxicity, toxicity in vivo after several administrations.•We investigate bio-distribution of COMRs in tissues and organs.•We investigate metabolism of complex using XPS, FT-IR.In this paper, drug-like properties of two series of carbonyl metal CO-releasing molecules, Ru(CO)3ClnL (n = 1, L = amino acid or its derivatives 1–7, L = acetylacetone 8 or 2,2′-bipyridyl 9; n = 2, L = aminopyridine derivatives 10–13; n = 0, L = salicylaldehyde Schiff base 14–15) and M(CO)5L(M = Cr, Mo, W; L = glycine methyl ester 16–18; L = N-methyl imidazole 19–21), were preliminarily evaluated from four aspects involving in cytotoxicity, in vivo toxicity, bio-distribution and metabolism. Cytotoxic effects of all complexes were assayed by MTT. IC50 values of complexes 1–15 were 39.55–240.16 mg/l, and those of complexes 16 and 18 were 21.36–22.21 mg/l. Toxicity tests of mice used oral acute toxic class method and got LD50 values of some complexes; among them, LD50 of complex 1 was in 800–1000 mg/kg, complex 7 in 1100–1500 mg/kg and complex 18 in 75–125 mg/kg. After several consecutive administrations, tested complexes severely damaged liver and kidney in both functional and morphological aspects. And by metal ions measurements using ICP-AES, we found that the tested complexes were unevenly distributed in tissues and organs. In vivo, RuII in complexes was oxidized to RuIII by P450 enzymes, and for Mo0 and W0 in complexes, part of them transformed into higher oxidation state, the others kept original state.

Syntheses, toxicity and biodistribution of CO-releasing molecules containing M(CO)5 (M=Mo, W and Cr)

Co-reporter:Huapeng Liu;Pengpeng Wang;Yonglin Chen;Bin Liu;Baoping Zhang;Qian Zheng

Applied Organometallic Chemistry 2014 Volume 28( Issue 3) pp:169-179

Publication Date(Web):

DOI:10.1002/aoc.3105

A series of CO-releasing molecules M(CO)₅ L (M = Mo, W and Cr), (1–3, L = glycine methyl ester; 4–6, N-methylimidazole; 7–9, 2-aminopyridine; 10–12, 3-aminopyridine; 13–15, 4-aminopyridine), were synthesized. All complexes have been characterized by NMR, IR and electrospray ionization mass spectroscopy; the octahedral structures of 14 and 15 were also established by X-ray crystallography. Furthermore, all complexes were evaluated for toxicity, pharmacokinetics and metabolic processes. Cytotoxic effects on the proliferation of fibroblast cell line were assayed by MTT. Among the complexes, Mo complex 1 showed the lowest cytotoxicity (IC₅₀ = 597 µmol l⁻¹) and W complex 2 showed a remarkable toxic effect, with IC₅₀ = 52 µmol l⁻¹. With the same ligand, the toxic effects of the complexes increase in the order of metal element W < Cr < Mo. For the same central metal element, the complexes containing imidazole showed lower toxic effects than those containing amino acid ester or aminopyridine. In accordance with the results from cytotoxicity, the complexes also showed corresponding toxic effects in animal models. The biodistributions of the complexes were established by inductively coupled plasma–atomic emission spectroscopy, measuring metal in tissues and organs. The results show that the complexes were gradually absorbed and unevenly distributed in vivo. The complexes containing imidazole entered tissues and organs faster than those containing amino acid ester. The complexes containing W atom were absorbed and distributed more slowly than those containing Mo or Cr atoms. Copyright © 2014 John Wiley & Sons, Ltd.

Aerobic oxidation of secondary alcohols using NHPI and iron salt as catalysts at room temperature

Co-reporter:Hanqing Zhao, Wei Sun, Chengxia Miao, Quanyi Zhao

Journal of Molecular Catalysis A: Chemical 2014 Volume 393() pp:62-67

Publication Date(Web):1 November 2014

DOI:10.1016/j.molcata.2014.06.007

•A new system including NHPI/Fe(NO3)3·9H2O for oxidation of alcohols was developed.•The system was suitable for secondary benzyl and aliphatic alcohols, up to 92% yield.•The reaction took place at room temperature under 1 atm oxygen.•A free-radical mechanism for NHPI/Fe(NO3)3·9H2O/O2 oxidation of alcohols is proposed.Aerobic oxidation of various alcohols has been accomplished by using a novel catalytic system, N-hydroxyphthalimide (NHPI) combined with Fe(NO3)3·9H2O. Secondary alcohols, especially benzylic and aliphatic alcohols, were smoothly transformed into corresponding ketones with up to 92% yields at room temperature under one atmosphere pressure of oxygen. The influences of reaction conditions such as solvent, different metal catalyst, catalyst loading and the structure of alcohols on the promotion effect were studied. And a possible radical mechanism for the oxidation of secondary alcohols in Fe(NO3)3·9H2O/NHPI/O2 system was proposed.

Resolution of chiral metal tetrahedral compounds through transamidation or transacetylation using lipase as a catalyst

Co-reporter:Quanyi Zhao, Bin Hu, Yuhua Zhang, Wenzhi Li, Chungu Xia, Yuanqi Yin

Tetrahedron: Asymmetry 2009 Volume 20(Issue 11) pp:1235-1238

Publication Date(Web):19 June 2009

DOI:10.1016/j.tetasy.2009.05.005

Highly enantiomerically pure tetrahedral metal compounds were obtained by transamidation catalyzed by a lipase. Meanwhile another tetrahedral type compound with high enantiomeric excess (92.62%) was also obtained by transacetylation catalyzed by lipase.High optically pure tetrahedral metal compounds were obtained by transamidation catalyzed by lipase. Meanwhile another type of tetrahedral compound with high ee value was also obtained first by transacetylation catalyzed by lipase. Ee value arrives in 92.62%.C15H7O10CoRuSW[Φ]D19=-154.4 (c 0.03, CH2Cl2)C15H7O10CoRuSeW[Φ]D19=-1003.4 (c 0.05, CH2Cl2)C15H7O10CoRuSeMo[Φ]D19=-1014.7 (c 0.05, CH2Cl2)C17H12O9NCoRuSW[Φ]D19=+2483.0 (c 0.025, CH2Cl2)C17H12O9NCoRuSeW[Φ]D19=-1086.6 (c 0.05, CH2Cl2)C17H12O9NCoRuSeMo[Φ]D19=+282.5 (c 0.05, CH2Cl2)C15H11O7CoW[Φ]D19=+1048.3 (c 0.05, CH2Cl2)Absolute configuration: (R)C17H13O8CoW[Φ]D19=-68.2 (c 0.05, CH2Cl2)Absolute configuration: (S)

Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method

Co-reporter:Yali Chen, Qian Yan, Mei Zhong, Quanyi Zhao, Junxi Liu, Duolong Di, Jinxia Liu

Acta Pharmaceutica Sinica B (May 2015) Volume 5(Issue 3) pp:238-245

Publication Date(Web):May 2015

DOI:10.1016/j.apsb.2015.03.012