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New dimeric carbazole-benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer

Maji, Basudeb and Kumar, Krishan and Muniyappa, K and Bhattacharya, Santanu (2015) New dimeric carbazole-benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer. In: ORGANIC & BIOMOLECULAR CHEMISTRY, 13 (30). pp. 8335-8348.

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Official URL: http://dx.doi.org/10.1039/c5ob00675a

Abstract

for selectively targeting cancer cells. Herein, we report the design and evolution of a new kind of carbazole-based benzimidazole dimers for their efficient telomerase inhibition activity. Spectroscopic titrations reveal the ligands high affinity toward the G4 DNA with significantly higher selectivity over duplex-DNA. The electrophoretic mobility shift assay shows that the ligands efficiently promote the formation of 04 DNA even at a lower concentration of the stabilizing K+ ions. The TRAP-LIG assay demonstrates the ligand's potential telomerase inhibition activity and also establishes that the activity proceeds via G4 DNA stabilization. An efficient nuclear internalization of the ligands in several common cancer cells (HeLa, HT1080, and A549) also enabled differentiation between normal HFF cells in co-cultures of cancer and normal ones. The ligands induce significant apoptotic response and antiproliferative activity toward cancer cells selectively when compared to the normal cells.

Item Type: Journal Article
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
Division of Chemical Sciences > Organic Chemistry
Depositing User: Id for Latest eprints
Date Deposited: 19 Aug 2015 07:07
Last Modified: 19 Aug 2015 07:07
URI: http://eprints.iisc.ac.in/id/eprint/52164

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