ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

Specific stabilization of promoter G-Quadruplex DNA by 2,6-disubstituted amidoanthracene-9,10-dione based dimeric distamycin analogues and their selective cancer cell cytotoxicity

Roy, S and Ali, A and Kamra, M and Muniyappa, K and Bhattacharya, S (2020) Specific stabilization of promoter G-Quadruplex DNA by 2,6-disubstituted amidoanthracene-9,10-dione based dimeric distamycin analogues and their selective cancer cell cytotoxicity. In: European Journal of Medicinal Chemistry, 195 .

[img] PDF
eur_jou_med_che_195_2020.pdf - Published Version
Restricted to Registered users only

Download (3MB) | Request a copy
[img] PDF
1-s2.0-S0223523420301690-mmc1.pdf - Published Supplemental Material
Restricted to Registered users only

Download (1MB) | Request a copy
Official URL: https://dx.doi.org/10.1016/j.ejmech.2020.112202

Abstract

We have designed and synthesized anthraquinone containing compounds which have oligopyrrole side chains of varying lengths. These compounds stabilized the G-quadruplex DNA formed in the promoter regions of c-MYC oncogenes selectively over the duplex DNA. These observations were recorded using UV�vis spectroscopic titrations, fluorescence measurements and circular dichroism (CD) spectral titrations. The potency of the compounds to stabilize the G4 DNA has been shown from the thermal denaturation experiments. The compound interacts with c-MYC G-quadruplex DNA through stacking mode as obtained from ethidium bromide displacement assay, cyclic voltammetric titration, and docking experiments. Molecular modeling studies suggested that the stacking of the anthraquinone moiety over the G-tetrad of the G4 structures are responsible for the stability of such quadruplex secondary structure. Furthermore, polymerase stop assay also supported the formation of stable G4 structures in the presence of the above-mentioned compounds. The compounds have shown selective cancer cell (HeLa and HEK293T) cytotoxicity over normal cells (NIH3T3 and HDFa) under in vitro conditions as determined from MTT based cell viability assay. Apoptosis was found to be the mechanistic pathway underlying the cancer cell cytotoxicity as obtained from Annexin V-FITC and PI dual staining assay which was further substantiated by nuclear morphological changes as observed by AO/EB dual staining assay. Cellular morphological changes, as well as nuclear condensation and fragmentation upon treatment with these compounds, were observed under bright field and confocal microscopy. © 2020

Item Type: Journal Article
Publication: European Journal of Medicinal Chemistry
Publisher: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Additional Information: The copyright of this article belongs to ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Organic Chemistry
Date Deposited: 10 Aug 2020 05:54
Last Modified: 10 Aug 2020 05:54
URI: http://eprints.iisc.ac.in/id/eprint/65216

Actions (login required)

View Item View Item