The pyrimidinetrione amide scaffold is cidal against replicating, as well as nonreplicating, M. tuberculosis
in vitro and ex vivo. (A) Kill kinetics of compound 10 against M. tuberculosis during active replication in vitro compared to negative (DMSO) and positive (5 μg/ml rifampin [RIF]) controls. (B) Anaerobic cidal activities of compounds 9, 10, and 20 compared to negative (untreated, DMSO, and 1 μg/ml isoniazid [INH]) and positive (100 μM metronidazole) controls after 7 days of compound exposure. M, metronidazole; U, untreated (control); D, DMSO; 10×, 10-fold MIC concentration isoniazid. (C) Efficacies of compounds 1, 9, 10, and 16 during growth of M. tuberculosis in J774 macrophages compared to the negative (DMSO) and positive (0.5 and 5 μg/ml RIF) controls. The horizontal bar indicates inoculum (day 0). The error bars indicate SD.