1H-Benzo[d]imidazoles and 3,4-dihydroquinazolin-4-ones: Design, synthesis and antitubercular activity.
Eur J Med Chem
; 155: 153-164, 2018 Jul 15.
Article
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| MEDLINE
| ID: mdl-29885576
ABSTRACT
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⯵M 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 IC50sâ¯>â¯30⯵M. 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⯵M and 0.94⯵M 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bencimidazoles
/
Quinazolinonas
/
Mycobacterium tuberculosis
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Antituberculosos
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2018
Tipo del documento:
Article