Thromboembolic complications represent a substantial problem in patients with atrial fibrillation （AF）. The prevalence of AF burden and associated arterial and venous thrombosis progressively increases with age. At ...Thromboembolic complications represent a substantial problem in patients with atrial fibrillation （AF）. The prevalence of AF burden and associated arterial and venous thrombosis progressively increases with age. At the same time, representative national data regarding stroke incidence in AF patients aged 80 and older are limited.展开更多
A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spect...A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.展开更多
文摘Thromboembolic complications represent a substantial problem in patients with atrial fibrillation （AF）. The prevalence of AF burden and associated arterial and venous thrombosis progressively increases with age. At the same time, representative national data regarding stroke incidence in AF patients aged 80 and older are limited.
基金supported by the National Natural Science Foundation of China(21672173,21372186)Research Fund for International Young Scientists from International(Regional)Cooperation and Exchange Program of NSFC(81650110529)+3 种基金Chongqing Special Foundation for Postdoctoral Research Proposal(Xm2016039,Xm2017185)Program for Overseas Young Talents from State Administration of Foreign Experts Affairs,China(WQ2017XNDX047)the Doctoral Fund of Southwest University(SWU111075)the Research Funds for the Central Universities(XDJK2017B015)
文摘A series of natural berberine-derived nitroimidazoles as novel antibacterial agents were designed, synthesized and characterized by nuclear magnetic resonance(NMR), infrared spectra(IR), and high resolution mass spectra(HRMS) spectra. The antimicrobial evaluation showed that some target molecules exhibited moderate to good inhibitory activities against the tested bacteria and fungi including clinical drug-resistant strains isolated from infected patients. Especially, 2-fluorobenzyl derivative8 f not only gave strong activity against drug-resistant E. coli with the minimal inhibitory concentration(MIC) value of0.003 m M, 33-fold more active than norfloxacin, but also exhibited low toxicity toward RAW 264.7 cells and less propensity to trigger resistance. The aqueous solubility and Clog P values of target compounds were investigated to elucidate the structureactivity relationships. Molecular docking and quantum chemical studies for compound 8 f rationally explained its antibacterial effect. The further exploration of antibacterial mechanism revealed that the highly active compound 8 f could effectively permeabilize E. coli cell membrane and intercalate into DNA isolated from resistant E. coli to form 8 f-DNA complex that might block DNA replication to exert the powerful bioactivities. Compound 8 f could also selectively address resistant E. coli from a mixture of various strains.
