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Triple targeting of mutant EGFRL858R/T790M, COX-2, and 15-LOX: design and synthesis of novel quinazolinone tethered phenyl urea derivatives for anti-inflammatory and anticancer evaluation
Faculty
Pharmacy
Year:
2023
Type of Publication:
ZU Hosted
Pages:
Authors:
Ahmed Samy Abdelsamad Abdelkhalek hilal
Staff Zu Site
Abstract In Staff Site
Journal:
Journal of Enzyme Inhibition and Medicinal Chemistry Taylor and francis
Volume:
Keywords :
Triple targeting , mutant EGFRL858R/T790M, COX-2, , 15-LOX:
Abstract:
We designed and synthesised novel quinazolinone tethered phenyl urea derivatives (6a–p) that triple target the double mutant EGFRL858R/T790M, COX-2, and 15-LOX. Compounds (6e, 6d, 6j, 6m, and 6n) not only had low micromolar IC50 inhibitory activities against the three targets, but they also showed good selectivity for COX-2 over COX-1 and for EGFRL858R/T790M over wild-type EGFR. Except for 6e and 6n, all of the tested compounds inhibited the NO production significantly more potently than celecoxib, diclofenac, and indomethacin. Compounds 6i and 6k reduced ROS levels more effectively than celecoxib and diclofenac. In terms of inhibiting TNF-α production, 6o-treated cells showed TNF-α level, which is ∼10 times lower than celecoxib. Furthermore, 6e and 6j had the highest anticancer activity against the breast cancer cell line BT-459 with growth inhibition percentages of 67.14 and 70.07%, respectively. Docking studies confirm their favoured binding affinity. The proposed compounds could be promising multi-targeted leads.
Author Related Publications
Ahmed Samy Abdelsamad Abdelkhalek hilal, "SYNTHESIS AND EVALUATION OF 2, 3-DIHYDROQUINAZOLIN-4(1H)-ONE DERIVATIVES AS ANALGESIC AND ANTI-INFLAMMATORY AGENTS", international, 2013
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Ahmed Samy Abdelsamad Abdelkhalek hilal, "Synthesis and biological screening of new derivatives of 2,3-dihydro quinazolin-4(1H)-one and benzotriazepin- 5(2H)-one for central nervous system activity", international, 2014
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Ahmed Samy Abdelsamad Abdelkhalek hilal, "“Methylene Bridge” to 5-HT3 Receptor Antagonists Conformationally Constrained Phenylguanidines", American Chemical Society, 2018
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Ahmed Samy Abdelsamad Abdelkhalek hilal, "Probing of 2-Amino-6-Chloro-3,4-Dihydroquinazoline Hydrochloride At 5- HT3 Receptor", Scholars Research Library, 2018
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Ahmed Samy Abdelsamad Abdelkhalek hilal, "Probing of 2-Amino-6-Chloro-3,4-Dihydroquinazoline Hydrochloride At 5- HT3 Receptor", Scholars Research Library, 2018
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Department Related Publications
Hassan Mahmoud Mohamed Elfayomy , "Pharmacological Studies on the Possible Interaction between some psychotropics& ", لايوجد, 1900
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Rasha Hassan Abdelghani Hassan , "Does vitamin B]&6 modulate the hypolipidemic effect of complamin,", لايوجد, 1900
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