Synthesis of new C-dimethylated chalcones as potent antitubercular agents

A new class of C-dimethylated-chalcones (9a-q) were synthesized by using 2-hydroxy-3,5-dimethyl-4,6-dimethoxy acetophenone as a key intermediate. The compounds were screened for anti-tubercular activity against Mycobacterium tuberculosis strain (H(37)Rv) by Microplate Alamar Blue assay (MABA) method at a concentration of 100-0.8 A mu g/mL. The chalcones, 9a, 9b, 9c, 9k, 9o, and 9p were found to have higher antitubercular activity than the standard drugs, while the remaining compounds showed moderate activity. The antitubercular activity of the chalcones, 9b (MIC90 = 3.98 A mu M) and 9o (MIC90 = 3.84 A mu M) was found to be more than two-fold more active than the standard drugs, streptomycin (MIC90 = 10.75 A mu M) and ciprofloxacin (MIC90 = 9.43 A mu M), while their antitubercular activity was found to be more than six-fold more active than pyrazinamide (MIC90 = 25.38 A mu M). Further, the molecular docking studies employing Mycobacterium tuberculosis protein tyrosine phosphatase (MtbPtp) was carried out to observe docking scores.