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
Author(s)
Thanh Nguyen Le[Thanh Nguyen Le]양수희[양수희]Daulat Bikram Khadka[Daulat Bikram Khadka]Hue Thi My Van[Hue Thi My Van]조숙희[조숙희]권영주[권영주]이응석이경태[이경태]조원제[조원제]
Keywords
MEDIATED DNA CLEAVAGE; DRUG CAMPTOTHECIN; ANTICANCER AGENTS; ANTITUMOR AGENTS; DOCKING; 3-ARYLISOQUINOLINES; DERIVATIVES; INDUCTION; COMPLEX; POTENT
Issue Date
201107
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOORGANIC & MEDICINAL CHEMISTRY, v.19, no.14, pp.4399 - 4404
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. (C) 2011 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/24849http://dx.doi.org/10.1016/j.bmc.2011.05.012
ISSN
0968-0896
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약학대학 > 약학부 > Articles
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