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Substituted 2-arylquinazolinones: Design, synthesis, and evaluation of cytotoxicity and inhibition of topoisomerases
- Substituted 2-arylquinazolinones: Design, synthesis, and evaluation of cytotoxicity and inhibition of topoisomerases
- Khadka, Daulat Bikram; Giap Huu Tran; Shin, Somin; Hang Thi Minh Nguyen; Hue Thi Cao; Zhao, Chao; Jin, Yifeng; Hue Thi My Van; Minh Van Chau; Kwon, Youngjoo; Thanh Nguyen Le; Cho, Won-Jea
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
- EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY vol. 103, pp. 69 - 79
- 2-Arylquinazolinone; 3-Arylisoquinoline; Topoisomerase; Cytotoxicity; Molecular docking
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- SCIE; SCOPUS
- Document Type
- A series of 2-arylquinazolinones with structural homology to known 3-arylisoquinolines were designed and synthesized in order to develop safe, effective, and selective cytotoxic agents targeting top-oisomerases (topos). 2-Arylquinzolinones with various substitutions on the aromatic rings were obtained by thermal cyclodehydration/dehydrogenation on reacting anthranilamides and benzaldehydes. The compounds had superior topo I-inhibitory activities but were generally inactive against topo II alpha. Among the 6-methyl-, 6-amino-, and 7-methylquinazolinones, 6-amino-substituted derivatives displayed potent cytotoxicity at submicromolar to nanomolar concentrations against human colorectal adenocarcinoma cells (HCT-15), human ductal breast epithelial tumor cells (T47D), and cervical cancer cells (HeLa). There was a good correlation between topo I inhibition and the cytotoxic effects of 6-aminoquinazolinones. Docking models demonstrated that topo I inhibition by these compounds is owing to intercalation and H-bond interactions with the DNA bases and amino acid residues at the enzymatic site. (C) 2015 Elsevier Masson SAS. All rights reserved.
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