Synthesis and evaluation of chromenyl barbiturates and thiobarbiturates as potential antitubercular agents.

A novel series of barbiturate and thiobarbiturate analogs of 2-benzoyl-3-methyl-5-oxo-5H-furo[3,2-g]chromene-6-carbaldehydes (3a-g and 4a-d, respectively) and 6-methyl-4,8-dioxo-4,8-dihydropyrano[3,2-g]chromenes (7a-c), were synthesized and evaluated for their antitubercular activities against Mycobacterium tuberculosis H37RV, and cytotoxicity (CC(50)) in the VERO cell MABA assay. The results indicate that the furanochromene series of compounds (3a-g and 4a-d) showed only weak to moderate antitubercular activity. However, the pyranochromene analog 7b showed good antitubercular activity (IC(90): 5.9μg/mL) and cytotoxicity (CC(50): 14.27μg/mL). The antitubercular activity of 7b was superior to the antituberculosis drug, pyrazinamide (PZA; IC(90): >20μg/mL). Analog 7b was considered to be a lead compound for subsequent structural optimization.