Design and synthesis of novel 1-substituted -3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea analogues targeting on TACE, as potent anticancer agents
1 Bharati Vidyapeeth (Deemed to be University), Poona College of Pharmacy, Kothrud, Pune-411038, Maharashtra, India.
2 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth (Deemed to be University), Poona College of Pharmacy, Kothrud, Pune-411038, Maharashtra, India.
Research Article
GSC Biological and Pharmaceutical Sciences, 2020, 12(02), 194-205.
Article DOI: 10.30574/gscbps.2020.12.2.0255
Publication history:
Received on 01 August 2020; revised on 10 August 2020; accepted on 11 August 2020
Abstract:
1-substituted phenyl quinazolinones analogues were designed by performing molecular modelling studies against tumour necrosis factor alpha converting enzyme (TACE PDB Id: 2A8H) and in-silico Lipinski properties for drug likeness. From QSAR studies, it could be concluded that the urea and thiourea groups play a crucial role in enhancing cytotoxic effects of compounds. Substitution of halogens like trifluoromethyl, chloro and allylic functional group may enhance the cytotoxic effect of urea and thiourea analogues. Substitution of phenyl and benzoyl ring were not found effective against cancer. Also, the presence of substituted aromatic ring at position 3 and methyl or thiol group at position 2 are essential for antimicrobial activities of quinazolinone. The synthesized compounds were characterized by TLC, MP, IR, NMR and Mass spectral data and were screened for their anticancer activity. The in vitro anticancer studies were performed on six selected compounds using MTT assay against MDA MB-231 cell line using paclitaxel as a standard. The synthesized 1-substituted -3-(4-oxo-2-phenylquinazolin-3(4h)-yl) urea and thiourea derivatives exhibited significant anticancer activities.
Keywords:
Anticancer; MDA-MB 231; MTT assay; Quinazolinone analogues; TACE
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