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Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer

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posted on 2024-07-25, 15:54 authored by Hanan A Henidi, Ahmed M. Al-Abd, Fahad Al-Abbasi, Hawazen A BinMahfouz, Ibrahim M El-Deeb

New phenylaminopyrimidine (PAP) derivatives have been designed and synthesised as potential tyrosine kinase inhibitors for the treatment of cancer. The synthesized compounds share a general structure and vary in the substitution pattern at position-2 of the pyridine ring. Several derivatives have demonstrated potent anticancer activities against HCT-116, HT-29 and LS-174T colorectal cancer cells. Furthermore, a number of hits showed good selectivity to Src-kinase. The cytotoxic mechanisms of these compounds were also investigated by studying their effects on cell-cycle distribution. Among all the compounds examined, compound 8b (with a terminal pyridin-3-yl moiety at the pyridine ring) showed the highest inhibitory selectivity towards src-kinase, which was coupled with cell cycle arrest, and apoptotic and autophagic interference, in colorectal cancer cells. This report introduces a novel category of PAP derivatives with promising kinase inhibitory and anticancer effects against colon cancer. 

Funding

Royal College of Surgeons in Ireland-Medical University of Bahrain (Grant number BR00063)

History

Comments

The original article is available at https://pubs.rsc.org/

Published Citation

Henidi HA, Al-Abd AM, Al-Abbasi FA, BinMahfouz HA, El-Deeb IM. Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer. RSC Adv. 2019;9(37):21578-21586.

Publication Date

11 July 2019

PubMed ID

35521305

Department/Unit

  • RCSI Bahrain

Publisher

Royal Society of Chemistry

Version

  • Published Version (Version of Record)