Design, synthesis and biological evaluation of alkynyl-containing maleimide derivatives for the treatment of drug-resistant tuberculosis

A series of alkynyl-containing maleimides with potent anti-tuberculosis (TB) activity was developed through a rigid group substitution strategy based on our previous study. Systematic optimization of the two side chains flanking the maleimide core led to new compounds with potent activity against Mycobacterium tuberculosis (MIC < 1 mu g/mL) and low cytotoxicity (IC50 > 64 mu g/mL). Among them, compound 29 not only possessed good ac-tivity against extensively drug-resistant TB and favorable hepatocyte stability, but also displayed good intra-cellular antimycobacterial activity in macrophages. This study lays a good foundation for identifying new alkynyl-containing maleimides as promising leads for treating drug-resistant TB.