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Synthesis and biological evaluation of novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid derivatives and their precursors as antileukemic agents

Gowda, NR Thimme and Kavitha, CV and Chiruvella, Kishore K and Joy, Omana and Rangappa, Kanchugarakoppal S. and Raghavan, Sathees C (2009) Synthesis and biological evaluation of novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid derivatives and their precursors as antileukemic agents. In: Bioorganic & Medicinal Chemistry Letters, 19 (16). pp. 4594-4600.

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Abstract

We report here the synthesis and preliminary evaluation of novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid derivatives 6(a–k) and their precursors 5(a–k) as potential chemotherapeutic agents. In each case, the structures of the compounds were determined by FTIR, 1H NMR and mass spectroscopy. Among the synthesized molecules, methyl 1-(4-methoxyphenethyl)-2-(4-fluoro-3-nitrophenyl)-1H-benzimidazole-5-carboxylate (5a) induced maximum cell death in leukemic cells with an IC50 value of 3 μM. Using FACS analysis we show that the compound 5a induces S/G2 cell cycle arrest, which was further supported by the observed down regulation of CDK2, Cyclin B1 and PCNA. The observed downregulation of proapoptotic proteins, upregulation of antiapoptotic proteins, cleavage of PARP and elevated levels of DNA strand breaks indicated the activation of apoptosis by 5a. These results suggest that 5a could be a potent anti-leukemic agent.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier Science.
Keywords: Benzimidazole-5-carboxylic acid;Anticancer drugs; Chemotherapy;Cancer therapeutics;Apoptosis; DNA damage.
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 22 Dec 2009 06:56
Last Modified: 19 Sep 2010 05:41
URI: http://eprints.iisc.ernet.in/id/eprint/22282

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