Substituted 2-arylquinazolinones: Design, synthesis, and evaluation of cytotoxicity and inhibition of topoisomerases

Daulat Bikram Khadka, Giap Huu Tran, Somin Shin, Hang Thi Minh Nguyen, Hue Thi Cao, Chao Zhao, Yifeng Jin, Hue Thi My Van, Minh Van Chau, Youngjoo Kwon, Thanh Nguyen Le, Won Jea Cho

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19 Scopus citations


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 topoisomerases (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 IIα. 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.

Original languageEnglish
Pages (from-to)69-79
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 20 Oct 2015

Bibliographical note

Funding Information:
This work was supported by Vietnam National Foundation for Science and Technology (NAFOSTED) (Grant: 104.99–2011.56 ) and by Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant: HI12C1640 ).

Publisher Copyright:
© 2015 Elsevier Masson SAS.


  • 2-Arylquinazolinone
  • 3-Arylisoquinoline
  • Cytotoxicity
  • Molecular docking
  • Topoisomerase


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