Synthesis and biological evaluation of 8-substituted berberine derivatives as novel anti-mycobacterial agents.

Abstract: 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 Mycobacterium tuberculosis (M. tuberculosis) strain H₃₇Rv. 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. [Copyright &y& Elsevier]