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


: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.


Bioorg Med Chem


Camacho J,Barazarte A,Gamboa N,Rodrigues J,Rojas R,Vaisberg A,Gilman R,Charris J




Has Abstract


2011-03-15 00:00:00














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    journal_title:Bioorganic & medicinal chemistry

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    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry

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    authors: Trávnícek Z,Mikulík J,Cajan M,Zboril R,Popa I

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    journal_title:Bioorganic & medicinal chemistry

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry

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    authors: Potowski M,Golz C,Strohmann C,Antonchick AP,Waldmann H

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry

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    authors: Bollu A,Hassan MK,Dixit M,Sharma NK

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ajduković JJ,Penov Gaši KM,Jakimov DS,Klisurić OR,Jovanović-Šanta SS,Sakač MN,Aleksić LD,Djurendić EA

    更新日期:2015-04-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Kazmierski W,Bifulco N,Yang H,Boone L,DeAnda F,Watson C,Kenakin T

    更新日期:2003-07-03 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lee CS,Allwine DA,Barbachyn MR,Grega KC,Dolak LA,Ford CW,Jensen RM,Seest EP,Hamel JC,Schaadt RD,Stapert D,Yagi BH,Zurenko GE,Genin MJ

    更新日期:2001-12-01 00:00:00

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    abstract::Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG-motifs in a particular sequence context activate vertebrate immune cells. We examined the significance of negatively charged internucleoside linkages in the flanking sequences 5' and 3' to the CpG-motif on immunostimulatory activity. Cell pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu D,Kandimalla ER,Zhao Q,Cong Y,Agrawal S

    更新日期:2001-11-01 00:00:00