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A novel benzimidazole derivative binds to the DNA minor groove and induces apoptosis in leukemic cells

Hegde, Mahesh and Kumar, Kothanahally S. Sharath and Thomas, Elizabeth and Ananda, Hanumappa and Raghavan, Sathees C and Rangappa, Kanchugarakoppal S (2015) A novel benzimidazole derivative binds to the DNA minor groove and induces apoptosis in leukemic cells. In: RSC ADVANCES, 5 (113). pp. 93194-93208.

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Official URL: http://dx.doi.org/10.1039/c5ra16605e


DNA minor groove binders are an important class of chemotherapeutic agents. These small molecule inhibitors interfere with various cellular processes like DNA replication and transcription. Several benzimidazole derivatives showed affinity towards the DNA minor groove. In this study we show the synthesis and biological studies of a novel benzimidazole derivative (MH1), that inhibits topoisomerase II activity and in vitro transcription. UV-visible and fluorescence spectroscopic methods in conjunction with Hoechst displacement assay demonstrate that MH1 binds to DNA at the minor groove. Cytotoxic studies showed that leukemic cells are more sensitive to MH1 compared to cancer cells of epithelial origin. Further, we find that MH1 treatment leads to cell cycle arrest at G2/M, at early time points in Molt4 cells. Finally multiple cellular assays demonstrate that MH1 treatment leads to reduction in MMP, induction of apoptosis by activating CASPASE 9 and CASPASE 3. Thus our study shows MH1, a novel DNA minor groove binder, induces cytotoxicity efficiently in leukemic cells by activating the intrinsic pathway of apoptosis.

Item Type: Journal Article
Publication: RSC ADVANCES
Additional Information: Copy right for this article belongs to the ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 03 Dec 2015 04:54
Last Modified: 03 Dec 2015 04:54
URI: http://eprints.iisc.ac.in/id/eprint/52856

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