- 5-Nitroimidazole-derived Schiff bases and their copper(II) complexes exhibit potent antimicrobial activity against pathogenic anaerobic bacteria
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In the present work a family of novel secnidazole-derived Schiff base compounds and their copper(II) complexes were synthesized. The antimicrobial activities of the compounds were evaluated against clinically important anaerobic bacterial strains. The compounds exhibited in vitro antibacterial activity against Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Parabacteroides distasonis and Fusubacterium nucleatum pathogenic anaerobic bacteria. Upon coordination to copper(II) the antibacterial activity significantly increased in several cases. Some derivatives were even more active than the antimicrobial drugs secnidazole and metronidazole. Therefore, the compounds under study are suitable for in vivo evaluation and the microorganisms should be classified as susceptible to them. Electrochemical studies on the reduction of the nitro group revealed that the compounds show comparable reduction potentials, which are in the same range of the bio-reducible drugs secnidazole and benznidazole. The nitro group reduction potential is more favorable for the copper(II) complexes than for the starting ligands. Hence, the antimicrobial activities of the compounds under study might in part be related to intracellular bio-reduction activation. Considering the increasing resistance rates of anaerobic bacteria against a wide range of antimicrobial drugs, the present work constitutes an important contribution to the development of new antibacterial drug candidates.
- Oliveira, Alexandre A.,Oliveira, Ana P. A.,Franco, Lucas L.,Ferencs, Micael O.,Ferreira, Jo?o F. G.,Bachi, Sofia M. P. S.,Speziali, Nivaldo L.,Farias, Luiz M.,Magalh?es, Paula P.,Beraldo, Heloisa
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- Indole nitroimidazole compound and preparation method and application thereof
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The invention relates to an indole nitroimidazole compound and a preparation method and application thereof and belongs to the technical field of chemical synthesis. The indole nitroimidazole compoundand officinal salt thereof are shown in the formulas I-VII, the compound has certain inhibitory activity on growth of gram positive bacteria, gram negative bacteria and fungi and can be used for preparing antibacterial and/or antifungal medicine, more safe and efficient diverse candidate medicine is provided for clinical antimicrobic treatment with a chance, and the compound helps to solve the clinical treatment problems of medicine resistance on the acceleration, stubborn pathogenicity microorganisms, emerging harmful microorganisms and the like. The preparation raw materials are simple, thecompound is low in price and easy to obtain, the synthetic route is short, and the compound has important significance in application of infection resistance. The formulas are shown in the description.
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Paragraph 0047-0050
(2019/01/23)
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- Discovery of novel nitroimidazole enols as Pseudomonas aeruginosa DNA cleavage agents
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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.
- Li, Zhen-Zhen,Gopala, Lavanya,Tangadanchu, Vijai Kumar Reddy,Gao, Wei-Wei,Zhou, Cheng-He
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p. 6511 - 6522
(2017/11/03)
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