Synthesis,antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues |
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| Authors: | Ibrahim A. Al-Suwaidan Alaa A.-M. Abdel-Aziz Taghreed Z. Shawer Rezk R. Ayyad Amer M. Alanazi Ahmad M. El-Morsy |
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| Affiliation: | 1. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia,;2. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia,;3. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt,;4. Department of Pharmaceutical Chemistry, and;5. Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt, |
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| Abstract: | A novel series of 3-benzyl-substituted-4(3H)-quinazolinones were designed, synthesized and evaluated for their in vitro antitumor activity. The results of this study demonstrated that 2-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide, 2-(3-benzyl-6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide and 3-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)-propanamide have shown amazing broad spectrum antitumor activity with mean GI50 (10.47, 7.24 and 14.12?µM. respectively), and are nearly 1.5–3.0-fold more potent compared with the positive control 5-FU with mean GI50, 22.60?µM. On the other hand, compounds 6 and 10 yielded selective activities toward CNS, renal and breast cancer cell lines, whereas compound 9 showed selective activities towards leukemia cell lines. Molecular docking methodology was performed for compounds 7 and 8 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib, while compound 11 into ATP binding site of B-RAF kinase inhibited the growth of melanoma cell lines through inhibition of B-RAF kinase, similar to PLX4032. |
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| Keywords: | 5-FU erlotinib in vitro antitumor evaluation molecular docking NCI quinazoline |
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