Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G-Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

Roy, S and Muniyappa, K and Bhattacharya, S (2022) Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G-Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity. In: ChemMedChem .

PDF che_med_che_2022.pdf - Published Version Restricted to Registered users only Download (8MB) | Request a copy

Abstract

Anthraquinone-based compounds are well-known as duplex DNA as well as G-quadruplex DNA binders. Implications of various anthraquinone derivatives for specific recognition of G-quadruplex DNA over duplex DNA is a ‘challenging’ research work that requires adequate experience with molecular design. To address this important issue, we designed and synthesized ten new 2,6-disubstituted anthraquinone-based derivatives with different functionalized piperazinyl side-chains. Among these, particular compounds with certain distant groups have shown selective and significant binding affinities toward the c-MYC and c-KIT G-quadruplex DNA over the duplex DNA, as noticed from various biophysical experiments. The structural difference of quadruplex and duplex DNA was utilized to probe these derivatives for the end-stacking mode of binding with G-quadruplex DNA. The ability of the ligands to halt DNA synthesis by stabilizing G-quadruplex structures is one of the crucial points to further apply them for quadruplex-mediated anti-cancer therapeutics. Interestingly, these ligands trigger apoptosis to exhibit selective cytotoxicity toward cancer cells over normal cells. This was further evidenced by ligand-induced cell cycle arrest as well as cellular apoptotic morphological changes. These blood-compatible ligands provided detailed structure-activity relationship approaches for the molecular design of anthraquinone-based G-quadruplex binders.

Item Type:	Journal Article
Publication:	ChemMedChem
Publisher:	John Wiley and Sons Ltd
Additional Information:	The copyright for this article belongs to John Wiley and Sons Ltd.
Keywords:	anthraquinone derivatives; cancer; G-quadruplex DNA; structure-activity relationships
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Chemical Sciences > Organic Chemistry
Date Deposited:	31 Oct 2022 08:59
Last Modified:	31 Oct 2022 08:59
URI:	https://eprints.iisc.ac.in/id/eprint/77656

Actions (login required)

View Item