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Design and synthesis of 4-amino-2-phenylquinazolines as novel topoisomerase i inhibitors with molecular modeling

Title
Design and synthesis of 4-amino-2-phenylquinazolines as novel topoisomerase i inhibitors with molecular modeling
Authors
Le T.N.Yang S.H.Khadka D.B.Van H.T.M.Cho S.H.Kwon Y.Lee E.-S.Lee K.-T.Cho W.-J.
Ewha Authors
권영주
SCOPUS Author ID
권영주scopus
Issue Date
2011
Journal Title
Bioorganic and Medicinal Chemistry
ISSN
0968-0896JCR Link
Citation
vol. 19, no. 14, pp. 4399 - 4404
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
4-Amino-2-phenylquinazolines 7 were designed as bioisosteres of 3-arylisoquinolinamines 6 that were energy minimized to provide stable conformers. Interestingly, the 2-phenyl ring of 4-amino-2-phenylquinazolines was parallel to the quinazoline ring and improved their DNA intercalation ability in the DNA-topo I complex. Among the synthesized 4-amino group-substituted analogs, 4-cyclohexylamino-2-phenylquinazoline 7h exhibited potent topo I inhibitory activity and strong cytotoxicity. Interestingly, consistency was observed between the cytotoxicities and topo I activities in these quinazoline analogs, suggesting that the target of 4-amino-2-phenylquinazolines is limited to topo I. Molecular docking studies were performed with the Surflex-Dock program to afford the ideal interaction mode of the compound into the binding site of the DNA-topo I complex in order to clarify the topo I activity of 7h. © 2011 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.bmc.2011.05.012
Appears in Collections:
약학대학 > 약학과 > Journal papers
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