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Int. J. Mol. Sci. 2018, 19(6), 1731; https://doi.org/10.3390/ijms19061731

Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects

1
Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia
2
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
3
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assuit 71526, Egypt
4
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
5
Department of Pharmaceutical and Medicinal Chemistry, Pharmacy College, Misr University for Science and Technology, Cairo 12568, Egypt
6
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 4 May 2018 / Revised: 1 June 2018 / Accepted: 6 June 2018 / Published: 11 June 2018
(This article belongs to the Section Molecular Biophysics)
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Abstract

A series of new fluoroquinazolinone 68 and 10ag derivatives was designed, prepared and screened for their in vitro cytotoxic activity against human cancer cell lines MCF-7 and MDA-MBA-231. Compounds 6 (IC50 = 0.35 ± 0.01 µM), 10f (IC50 = 0.71 ± 0.01 µM), 10d (IC50 = 0.89 ± 0.02 µM) and 10a (IC50 = 0.95 ± 0.01 µM) displayed broad spectrum anticancer activity better than the reference drug gefitinib (IC50 = 0.97 ± 0.02 µM) against MCF-7. Compounds 10e (IC50 = 0.28 ± 0.02 µM), 10d (IC50 = 0.38 ± 0.01 µM), 7 (IC50 = 0.94 ± 0.07 µM) and 10c (IC50 = 1.09 ± 0.01 µM) showed better activity than the reference gefitinib (IC50 = 1.30 ± 0.04 µM) against MDA-MBA-231. Moreover, EGFR and tubulin inhibition assays were performed for the highest active derivatives and showed remarkable results comparing to the reference drugs. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. View Full-Text
Keywords: design; fluoroquinazolinone; cytotoxicity; EGFR kinase; tubulin inhibitors design; fluoroquinazolinone; cytotoxicity; EGFR kinase; tubulin inhibitors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Zayed, M.F.; Ahmed, S.; Ihmaid, S.; Ahmed, H.E.A.; Rateb, H.S.; Ibrahim, S.R.M. Design, Synthesis, Cytotoxic Evaluation and Molecular Docking of New Fluoroquinazolinones as Potent Anticancer Agents with Dual EGFR Kinase and Tubulin Polymerization Inhibitory Effects. Int. J. Mol. Sci. 2018, 19, 1731.

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