Synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and antitubercular agents

José Camacho, Arthur Barazarte, Neira Gamboa, Juan Rodrigues, Rosario Rojas, Abraham Vaisberg, Robert Gilman, Jaime Charris

Research output: Contribution to journalArticlepeer-review

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 H37Rv 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.

Original languageEnglish (US)
Pages (from-to)2023-2029
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number6
DOIs
StatePublished - Mar 15 2011
Externally publishedYes

Keywords

  • Antimalarial
  • Benzimidazole
  • Cancer
  • Plasmodium berghei
  • Tuberculosis
  • β-Hematin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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