Design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives.

Abstract In an effort to develop novel potent antitubercular drugs, thirty-one oridonin derivatives were designed and prepared. All the compounds obtained were screened for their in vitro activities against Mycobacterium phlei , Mycobacterium smegmatis and Mycobacterium marinum . Among them, thirteen compounds showed significant inhibitory activity against M. phlei with MICs less than 2 μg/mL. Compounds 2k , 8d , 10c , 10d containing trans -cinnamic acid moiety were the most potent (MIC = 0.5 μg/mL), comparable to the well-known antitubercular drug streptomycin. The preliminary structure–activity relationships (SARs) were also analyzed.