Tuberculosis(TB)is a disease which kills two million people every year and infects over one-third of the world's population.Eighteen new 8-substituted berberine derivatives were synthesized and evaluated for their...Tuberculosis(TB)is a disease which kills two million people every year and infects over one-third of the world's population.Eighteen new 8-substituted berberine derivatives were synthesized and evaluated for their anti-mycobacterial activities against M ycobacterium tuberculosis(M.tuberculosis)strain H_(37)Rv.Among these compounds,compound 6i was the most effective antitubercular agent with an MIC of 1.0μg/mL.Most importantly,compound 6i also exhibited a potent effect against clinically isolated rifampicin-and isoniazid-resistant M.tuberculosis strains,suggesting a different mode of action from the current drugs.Therefore,it shows potential for the development of new anti-TB agents.展开更多
A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria.Compound 33a(IMBZ18G)is highly effective in vitro and in vivo against c...A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria.Compound 33a(IMBZ18G)is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant(MDR)Gram-negative strains,with a highly druglike nature.The checkerboard assay reveals its significant synergistic effect withβ-lactamase inhibitor avibactam,and the MIC values against MDR enterobacteria were reduced up to 4—512folds.X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and Cβ-lactamases.Accordingly,preclinical studies of 33a alone and 33a-avibactam combination as potential innovative candidates are actively going on,in the treatment ofβ-lactamase-producing MDR Gram-negative bacterial infections.展开更多
基金This work was supported by the National Natural Science Foundation for Young Scientists(81102312)the National S&T Major Special Projecton Major New Drug Innovation(2012ZX09301002-001-017).
文摘Tuberculosis(TB)is a disease which kills two million people every year and infects over one-third of the world's population.Eighteen new 8-substituted berberine derivatives were synthesized and evaluated for their anti-mycobacterial activities against M ycobacterium tuberculosis(M.tuberculosis)strain H_(37)Rv.Among these compounds,compound 6i was the most effective antitubercular agent with an MIC of 1.0μg/mL.Most importantly,compound 6i also exhibited a potent effect against clinically isolated rifampicin-and isoniazid-resistant M.tuberculosis strains,suggesting a different mode of action from the current drugs.Therefore,it shows potential for the development of new anti-TB agents.
基金supported by CAMS Innovation Fund for Medical Sciences(2021-12M-1-070)National Natural Science Foundation of China(32141003)。
文摘A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria.Compound 33a(IMBZ18G)is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant(MDR)Gram-negative strains,with a highly druglike nature.The checkerboard assay reveals its significant synergistic effect withβ-lactamase inhibitor avibactam,and the MIC values against MDR enterobacteria were reduced up to 4—512folds.X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and Cβ-lactamases.Accordingly,preclinical studies of 33a alone and 33a-avibactam combination as potential innovative candidates are actively going on,in the treatment ofβ-lactamase-producing MDR Gram-negative bacterial infections.
