3-Formylchromone based topoisomerase IIα inhibitors: discovery of potent leadsElectronic supplementary information (ESI) available. See DOI: 10.1039/c3md00125c

Substituted 3-formylchromones were synthesized and evaluated as inhibitors of the human DNA topoisomerase IIα (hTopo-IIα) enzyme. The results of the decatenation, relaxation and DNA intercalation assays revealed that the compounds ( 11b , 12a , 12b , 12d , 12e , 13a and 13b ) exhibited potent inhibi...

Full description

Saved in:
Bibliographic Details
Main Authors: Singh, Satyajit, Baviskar, Ashish Triambak, Jain, Vaibhav, Mishra, Nidhi, Chand Banerjee, Uttam, Bharatam, Prasad V, Tikoo, Kulbhushan, Singh Ishar, Mohan Paul
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Substituted 3-formylchromones were synthesized and evaluated as inhibitors of the human DNA topoisomerase IIα (hTopo-IIα) enzyme. The results of the decatenation, relaxation and DNA intercalation assays revealed that the compounds ( 11b , 12a , 12b , 12d , 12e , 13a and 13b ) exhibited potent inhibitory activity against the hTopo-IIα enzyme, and are nonintercalating agents. These compounds also possess significant in vitro cytotoxicity (LC 50 ranges from 0.5-8.6 μM) against prostate (PC-3) cancerous cell line as seen in comparison to the standard drug etoposide. To further probe the plausible mode of action of 3-formylchromone derivatives, molecular docking studies have also been carried out, which showed that the compounds under investigation fitted well in the ATP binding pocket of hTopo-IIα enzyme with good docking scores and form nonbonding interactions with the crucial residues of the catalytic site. Substituted 3-formylchromones were synthesized and evaluated as inhibitors of human the DNA topoisomerase IIα (hTopo-IIα) enzyme.
ISSN:2040-2503
2040-2511
DOI:10.1039/c3md00125c