Abstract:
:A series of N'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3H-benzo[d]imidazole-5-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit β-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent Plasmodium berghei. Selected analogues were screened for their antitubercular activity against sensitive MTB H(37)Rv and multidrug-resistant MDR-MTB strains, and cytotoxic activity against a panel of human tumor cell lines and two nontumourogenic cell lines. Compounds 3a, 5a, f, 6g were the most promising as inhibitors of β-hematin formation, however, their effect as inhibitors of hemoglobin hydrolysis were marginal. The most active compounds to emerge from the in vitro and in vivo murine studies were 3a and 6i, suggesting an antimalarial activity via inhibition of β-hematin formation and are as efficient as chloroquine. The cytotoxic and antitubercular activities of the present compounds were not comparable with those of the standard drugs employed. But, however, compound 5b showed better antitubercular activity compared to rifampin against multidrug-resistant MDR-MTB strains. Compounds 3a, 6i and 5b showed a good safety index.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Camacho J,Barazarte A,Gamboa N,Rodrigues J,Rojas R,Vaisberg A,Gilman R,Charris Jdoi
10.1016/j.bmc.2011.01.050subject
Has Abstractpub_date
2011-03-15 00:00:00pages
2023-9issue
6eissn
0968-0896issn
1464-3391pii
S0968-0896(11)00079-4journal_volume
19pub_type
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