Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold

Journal of Enzyme Inhibition and Medicinal Chemistry
Heba S A ElzahabiMay A El-Manawaty

Abstract

An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.

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Citations

Mar 21, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed El-NaggarMohamed A Al-Omar
Jul 30, 2019·Journal of Receptor and Signal Transduction Research·Maryam Tadayon, Zahra Garkani-Nejad
Jul 17, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Ismail M M OthmanElsayed A Elsayed
Jul 10, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Ismail M M OthmanAbd El-Galil E Amr
Sep 19, 2020·Chemical Biology & Drug Design·Pratibha Yadav, Kamal Shah
Jan 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Abd El-Galil E AmrMohamed M Abdallah
Nov 28, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eman S NossierSalwa M El-Hallouty
Oct 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eman M Mohi El-DeenEman S Nossier
Jan 1, 2021·Nucleosides, Nucleotides & Nucleic Acids·Mosselhi A M MohamedAdil A Gobouri
May 17, 2021·European Journal of Medicinal Chemistry·Adileh AyatiAlireza Foroumadi

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Methods Mentioned

BETA
X-ray

Software Mentioned

Molecular Operating Environment ( MOE® )
Molecular Operating Environment ( MOE
Kinexus

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