Browsing by Author "El-Sayed N.A."

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    New oxadiazoles with selective-COX-2 and EGFR dual inhibitory activity: Design, synthesis, cytotoxicity evaluation and in silico studies
    (Elsevier Masson SAS, 2019) El-Sayed N.A.; Nour M.S.; Salem M.A.; Arafa R.K.; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; Cairo University; Kasr El-Aini Street; Cairo; 11562; Egypt; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; October University of Modern Sciences and Arts (MSA); 6th; of October City; Giza; Egypt; Biomedical Sciences Program; Zewail City of Science and Technology; University of Science and Technology; October Gardens; 6th; of October City; Giza; 12578; Egypt; Drug Design and Discovery Laboratory; Helmy Institute of Science and Technology; Zewail City of Science and Technology; Cairo; 12578; Egypt
    Novel heterocyclic oxadiazoles viz. 2-subsituted-5-(4-pyridyl)-1,3,4-oxadiazoles, 2-subsituted-5-(3-pyridyl)-1,3,4-oxadiazoles and 2-subsituted-5-(phenyl or 4-chlorophenyl-1,3,4-oxadiazoles) were designed and synthesized as potential anticancer agents. In this investigation, all compounds were evaluated for their COX-1 and COX-2 inhibitory activity in vitro as new therapeutic approaches assumed cytotoxic effect associated with selective COX-2 inhibition. Results showed that most of the derivatives demonstrated inhibition towards both isoforms of COX comparable to the standard reference drugs indomethacin, diclofenac sodium and celecoxib. Then, nine selected compounds (IIId, VIb, VIIc, IX, XI, XIIa, XIVa, XVIb and XVIIIb) were subjected to cytotoxic screening against UO-31 renal cancer cell line using MTT assay. Compounds IIId, IX and XIIa displayed promising behavior by showing good anticancer activity. Moreover, kinase inhibitory assay against the tyrosine kinase EGFR was performed for the three compounds showing the highest cytotoxic activity. The tested compounds were potent against EGFR with the highest activity being observed for compound IX showing nearly double the potency of the reference drug Erlotinib. Moreover, molecular docking and molecular dynamics were performed for IIId, IX and XIIa against EGFR, in an attempt to elucidate a model for their binding at the molecular level, simulate and understand the possible binding interactions underlying the association between these small molecules and the kinase enzyme ATP binding pocket essential amino acids. Finally, in silico pharmacokinetic profile predication was investigated for IIId, IX and XIIIa using SWISS/ADME to identify the most promising small-molecule cytotoxic agent on the basis of displaying the best drug-like properties. Results indicated that compound IX has a potential to serve as a lead compound for developing novel anticancer therapeutic agents. � 2019 Elsevier Masson SAS
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    Novel heterocyclic-fused pyrimidine derivatives: Synthesis, molecular modeling and pharmacological screening
    (2013) Arafa R.K.; Nour M.S.; El-Sayed N.A.; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; Cairo University; Kasr El-Aini Street; Cairo 11562; Egypt; Department of Pharmaceutical Chemistry; Faculty of Pharmacy; MSA University; 6th October City; Cairo; Egypt
    Novel heterocyclic-fused pyrimidines viz pyrrolo[1,2-c]pyrimidines 4-8, pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines 9-14, pyrimido[4?,5?:4,5] pyrimido[1,6-a]azepines 16-18, pyrrolo[1?,2?:1,6]pyrimido[4,5-d][1, 3]thiazines 19a,b and 1,3-thiazino[4?,5?:4,5]pyrimido[1,6-a]-azepine 19c were designed and synthesized as potential anticancer agents. In this investigation all the newly synthesized compounds were subjected to cytotoxic screening against MCF-7 breast cancer cell line. Moreover, kinase inhibitory assay was done for compounds 5, 7, 9 and 18 against the non-receptor and receptor tyrosine kinases c-Src and VEGFR, respectively. The tested compounds were more potent against c-Src than VEGFR, and the highest activity was observed for 18 showing 81% c-Src activity inhibition. Finally, molecular docking was performed with c-Src and VEGFR in an attempt to simulate and understand the possible binding interactions underlying the association between these small molecules and the kinase enzyme ATP binding pocket essential amino acids. � 2013 Elsevier Masson SAS. All rights reserved.