Add time:07/15/2019         Source:sciencedirect.com

Using a classical hybridization approach, a series of 1H-benzo[d]imidazoles and 3,4-dihydroquinazolin-4-ones were synthesized (39 examples) and evaluated as inhibitors of Mycobacterium tuberculosis growth. Chemical modification studies yielded potent antitubercular agents with minimum inhibitory concentration (MIC) values as low as 0.24 μM against M. tuberculosis H37Rv strain. Further, the synthesized compounds were active against four drug-resistant strains containing different levels of resistance for the first line drugs. These molecules were devoid of apparent toxicity to HepG2, HaCat, and Vero cells with IC50s > 30 μM. Viability in mammalian cell cultures was evaluated using MTT and neutral red assays. In addition, some 3,4-dihydroquinazolin-4-ones showed low risk of cardiac toxicity, no signals of neurotoxicity or morphological alteration in zebrafish (Danio rerio) toxicity models. 3,4-Dihydroquinazolin-4-ones 9q and 9w were considered the lead compounds of these series of molecules with MIC values of 0.24 μM and 0.94 μM against M. tuberculosis H37Rv, respectively. Taken together, these data indicate that this class of compounds may furnish candidates for future development of novel anti-TB drugs.

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