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.
Original language | English |
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Pages (from-to) | 4399-4404 |
Number of pages | 6 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 19 |
Issue number | 14 |
DOIs | |
State | Published - 15 Jul 2011 |
Bibliographical note
Funding Information:This work was supported by Korea Research Foundation grant ( KRF-2009-0071379 ).
Keywords
- 4-Amino-2-phenylquinazolines
- Cytotoxicity
- DNA intercalation
- Docking study
- Topoisomerase I