Record Details

Targeting Promoter G-Quadruplex DNAs by Indenopyrimidine-Based Ligands

DSpace at IIT Bombay

View Archive Info
 
 
Field Value
 
Title Targeting Promoter G-Quadruplex DNAs by Indenopyrimidine-Based Ligands
 
Creator DIVESHKUMAR, KV
SAKRIKAR, S
HARIKRISHNA, S
DHAMODHARAN, V
PRADEEPKUMAR, PI
 
Subject DNA
G-quadruplexes
indenopyrimidines
promoters
specificity
POTENT TELOMERASE INHIBITOR
INTRAMOLECULAR G-QUADRUPLEX
C-MYC PROMOTER
GENOMIC PROMOTER
DESIGN
BINDING
DERIVATIVES
SEQUENCE
AGENTS
TELOMESTATIN
 
Description The formation of G-quadruplex structures can regulate telomerase activity and the expression of oncogenes at the transcriptional and translational levels. Therefore, stabilization of G-quadruplex DNA structures by small molecules has been recognized as a promising strategy for anticancer drug therapy. One of the major challenges in this field is to impart stabilizing molecules with selectivity toward quadruplex structures over duplex DNAs, and to maintain specificity toward a particular quadruplex topology. Herein we report the synthesis and binding interactions of indenopyrimidine derivatives, endowed with drug-like properties, with oncogenic promoters of c-myc and c-kit, telomeric and duplex DNAs. The results show specific stabilization of promoter over telomeric quadruplexes and duplex DNAs. Molecular modeling studies support the experimental observations by unraveling the dual binding mode of ligands by exploiting the top and bottom quartets of a G-quadruplex structure. This study underscores the potential of the indenopyrimidine scaffold, which can be used to achieve specific G-quadruplex-mediated anticancer activity.
 
Publisher WILEY-V C H VERLAG GMBH
 
Date 2014-12-28T15:10:25Z
2014-12-28T15:10:25Z
2014
 
Type Article
 
Identifier CHEMMEDCHEM, 9(12)2754-2765
1860-7179
1860-7187
http://dx.doi.org/10.1002/cmdc.201402394
http://dspace.library.iitb.ac.in/jspui/handle/100/16837
 
Language English