Design, Synthesis, QSAR, Molecular Docking Study and Antitumor Activity of some Novel Quinazolin-4(3H)-One Derivative

Z. Shawer, Taghreed; M. El-Sehrawi, Hend; E. Mansour, Reda

doi:10.18576/jpac/030210

Design, Synthesis, QSAR, Molecular Docking Study and Antitumor Activity of some Novel Quinazolin-4(3H)-One Derivative

Document Type : Original Article

Authors

Pharmaceutical Chemistry Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

10.18576/jpac/030210

Abstract

In view of the effective range of biological activities exhibited by quinazolines, a novel series of 2,3-disubstitutedquinazolin-4-(3H)-ones were designed, synthesized and evaluated for in vitro anticancer activity against human breast carcinoma cell line (MCF-7). The results of this study showed that 3-(4-aminophenyl)-2-(chloromethyl)quinazolin-4(3H)-one 2, 2-{[4-(2-chloromethyl-4-oxo-4H-quinazolin-3-yl)-phenyl]diazoenyl} malononitrile 11a, 2-(2,4-dichlorophenyl)-4-oxoquinazoline-3(4H)-carboxamide 16a and N-(2-(2,4-dichlorophenyl)-4-oxoquinazolin-3(4H)-yl) benzamide 18 possessed an inhibitory activity against human breast carcinoma with IC50 (2.84, 6.21, 4.19, and 2.48 ug/well) respectively. Compounds 2, 16a, and 18 were more potent compared with the positive control Imatinib with IC50, 6.06 ug/well. Molecular docking methodology was performed for compounds 2, 11a, 16a, and 18 into ATP binding site of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK), using gefitinib as a lead compound which proved that the docking results were in coincidence with the biological activity.

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