Browsing by Author "Kafafy A.-H.N."

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    Assessment of new anti-HER2 ligands using combined docking, QM/MM scoring and MD simulation
    (2013) Ahmed M.; Sadek M.M.; Serrya R.A.; Kafafy A.-H.N.; Abouzid K.A.; Wang F.; EChemistry Laboratory; Faculty of Life and Social Sciences; Swinburne University of Technology; Melbourne; VIC 3122; Australia; Pharmaceutical Organic Chemistry; Faculty of Pharmacy; MSA University; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; Ain Shams University; Cairo 11566; Egypt; Pharmaceutical Organic Chemistry Department; Faculty of Pharmacy; Assiut University; Egypt
    In the development of new anti-cancer drugs to tackle the problem of resistance to current chemotherapeutic agents, a new series of anti-HER2 (human epidermal growth factor receptors 2) agents has been synthesized and investigated using different computational methods. Although non-selective, the most active inhibitor in the new series shows higher activity toward HER2 than EGFR. The induced fit docking protocol (IFD) is performed to find possible binding poses of the new inhibitors in the active site of the HER2 receptor. Molecular dynamic simulations of the inhibitor-protein complexes for the two most active compounds from the new series are carried out. Simulations stability is checked using different stability parameters. Different scoring functions are employed. � 2012 Elsevier Inc.
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    Discovery of new HER2/EGFR dual kinase inhibitors based on the anilinoquinazoline scaffold as potential anti-cancer agents
    (Informa Healthcare, 2014) Sadek M.M.; Serrya R.A.; Kafafy A.-H.N.; Ahmed M.; Wang F.; Abouzid K.A.M.; Department of Pharmaceutical Organic Chemistry; Faculty of Pharmacy; MSA University; 6th October; Cairo; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; Ain Shams University; Cairo 11566; Egypt; Pharmaceutical Organic Chemistry Department; Faculty of Pharmacy; Assiut University; Abbassia; Cairo; Egypt; Chemistry Laboratory; Faculty of Life and Social Sciences; Swinburne University of Technology; Melbourne; VIC; Australia
    Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 4? position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 ?M, respectively, and with IC50 equal to 3.98 and 1.04 ?M on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 ?M, respectively. � 2014 Informa UK Ltd. All rights reserved.