Hegde, M. and Kumar, K. S. S. and Thomas, E. and Ananda, H. and Raghavan, S. C. and Rangappa, K. S. (2015) A novel benzimidazole derivative binds to the DNA minor groove and induces apoptosis in leukemic cells. RSC ADVANCES, 5 (113). pp. 93194-93208. ISSN 2046-2069
Full text not available from this repository. (Request a copy)Abstract
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: | Article |
|---|---|
| Subjects: | C Chemical Science > Chemistry |
| Divisions: | Department of > Chemistry |
| Depositing User: | Users 19 not found. |
| Date Deposited: | 18 Jun 2019 05:12 |
| Last Modified: | 18 Jun 2019 05:12 |
| URI: | http://eprints.uni-mysore.ac.in/id/eprint/3245 |
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