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Novel Quinazolin-4(3H)-One Linked to 1,2,3-Triazoles: Synthesis and Anticancer Activity Publisher Pubmed



Safavi M1 ; Ashtari A2 ; Khalili F3 ; Mirfazli SS4 ; Saeedi M5, 6 ; Ardestani SK3 ; Rashidi Ranjbar P2 ; Barazandeh Tehrani M7 ; Larijani B8 ; Mahdavi M8
Authors
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Authors Affiliations
  1. 1. Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, Iran
  2. 2. School of Chemistry, College of Science, University of Tehran, Tehran, Iran
  3. 3. Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran
  4. 4. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Chemical Biology and Drug Design Published:2018


Abstract

In this work, a wide range of novel quinazolin-4(3H)-one linked to 1,2,3-triazoles was designed, synthesized, and evaluated against a panel of three human breast (MDA-MB-231, MCF-7, T-47D), lung (A549), and prostate (PC3) cancer cell lines. Our results revealed that the anticancer activity of the synthesized compounds was selectively affected by the presence of methoxy group on the linker between quinazolinone and 1,2,3-triazole moieties. According to the calculated IC50 values, compounds 6q, 6w, and 6x showed good cytotoxicity against breast cancer cell lines even more effective than the reference drug, etoposide. Compounds 6q and 6u were found to be potent compounds against A549, non-small-cell lung cancer (NSCLC), comparing with erlotinib. Also, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that potent compounds induced apoptosis in human cancer cell lines. Molecular docking studies were performed to clarify the inhibition mode of compounds 6g, 6u, 6w, and 6x over the EGFR active site. The most promising compounds, 6q and 6u, possessing 3-methoxy group were well oriented to the gatekeeper hydrophobic pocket of EGFR active site and interact well with Ala719, Val702, and Leu820 through hydrophobic interaction. © 2018 John Wiley & Sons A/S.