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Molecules 2018, 23(7), 1699; https://doi.org/10.3390/molecules23071699

Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization

1
Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah 41477, Al-Munawarah, Saudi Arabia
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
3
Department of Pharmaceutical and Medicinal Chemistry, Pharmacy College, Misr University for Science and Technology, Cairo 12568, Egypt
4
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assuit 71526, Egypt
5
Department of Physical Therapy, College of Medical Rehabilitation Sciences, Taibah University, Al-Madinah 41477, Al-Munawarah, Saudi Arabia
6
Department of Basic Science, Faculty of Physical Therapy, Cairo University, Cairo 12613, Egypt
7
Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
*
Authors to whom correspondence should be addressed.
Received: 22 June 2018 / Revised: 4 July 2018 / Accepted: 9 July 2018 / Published: 12 July 2018
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [3229 KB, uploaded 12 July 2018]   |  

Abstract

Some fluoroquinazolinones (AH) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative G (IC50 = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC50 = 1.14 ± 0.04 µM) against MCF-7. New derivative E (IC50 = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC50 = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal growth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening. View Full-Text
Keywords: synthesis; fluoroquinazolinones; antitumor; EGFR inhibitor; tubulin inhibitor synthesis; fluoroquinazolinones; antitumor; EGFR inhibitor; tubulin inhibitor
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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.; Rateb, H.S.; Ahmed, S.; Khaled, O.A.; Ibrahim, S.R.M. Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization. Molecules 2018, 23, 1699.

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