Synthesis, structure–activity relationship and in vitro anti-mycobacterial evaluation of 13-n-octylberberine derivatives

Twenty-eight new 13-n-octylberberine derivatives were synthesized and evaluated for their activities against drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) strain H37Rv. Among these compounds, compound 16e was the most effective anti-tubercular agent with a MIC value of 0.125 μg/mL. Importantly, compound 16e exhibited more potent effect against rifampicin (RIF)- and isoniazid (INH)-resistant M. tuberculosis strains than both RIF and INH, suggesting a new mechanism of action. Therefore, it has been selected as a drug candidate for further investigation, or as a chemical probe for identifying protein target and studying tuberculosis biology. We consider 13-n-octylberberine analogs to be a promising novel class of antituberculars against multi-drug-resistant (MDR) strains of M. tuberculosis.

Graphical abstractA novel series of 13-substituted berberine derivatives have been identified as potent antimytobacterial agents against both drug-susceptible and MDR strains of Mycobacterium tuberculosis.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 13-n-Octylberberine analogs are a promising novel class of antituberculars. ► n-Octyl group at position 13 might be essential for the activity. ► Compound 16e exhibited a potential activity against MDR strains of M. tuberculosis.