Design, synthesis, and anti-cancer evaluation of new pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as potential EGFRWT and EGFRT790M inhibitors and apoptosis inducers

A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highe...

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Main Authors: Heba S. A. Elzahabi (Author), Eman S. Nossier (Author), Rania A. Alasfoury (Author), May El-Manawaty (Author), Sara M. Sayed (Author), Eslam B. Elkaeed (Author), Ahmed M. Metwaly (Author), Mohamed Hagras (Author), Ibrahim H. Eissa (Author)
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Published: Taylor & Francis Group, 2022-12-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Heba S. A. Elzahabi  |e author 
700 1 0 |a Eman S. Nossier  |e author 
700 1 0 |a Rania A. Alasfoury  |e author 
700 1 0 |a May El-Manawaty  |e author 
700 1 0 |a Sara M. Sayed  |e author 
700 1 0 |a Eslam B. Elkaeed  |e author 
700 1 0 |a Ahmed M. Metwaly  |e author 
700 1 0 |a Mohamed Hagras  |e author 
700 1 0 |a Ibrahim H. Eissa  |e author 
245 0 0 |a Design, synthesis, and anti-cancer evaluation of new pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as potential EGFRWT and EGFRT790M inhibitors and apoptosis inducers 
260 |b Taylor & Francis Group,   |c 2022-12-01T00:00:00Z. 
500 |a 10.1080/14756366.2022.2062752 
500 |a 1475-6374 
500 |a 1475-6366 
520 |a A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC50 screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFRWT and mutant EGFRT790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFRWT and EGFRT790M with IC50 values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFRWT and EGFRT790M. 
546 |a EN 
690 |a Anti-proliferative 
690 |a apoptosis 
690 |a docking studies 
690 |a EGFR inhibitors 
690 |a pyrido[2,3-d]pyrimidin-4(3H)-one 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 37, Iss 1, Pp 1053-1076 (2022) 
787 0 |n https://www.tandfonline.com/doi/10.1080/14756366.2022.2062752 
787 0 |n https://doaj.org/toc/1475-6366 
787 0 |n https://doaj.org/toc/1475-6374 
856 4 1 |u https://doaj.org/article/043a1c62528a44f39d1f4e0955ba4c9b  |z Connect to this object online.