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

• Published in: RSC advances Vol. 9; no. 37; pp. 21578 - 21586
• Main Authors: Henidi, Hanan A, Al-Abd, Ahmed M, Al-Abbasi, Fahad A, BinMahfouz, Hawazen A, El-Deeb, Ibrahim M
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 11.07.2019; The Royal Society of Chemistry
• Subjects: Anticancer properties; Antiproliferatives; Cell cycle; Chemistry; Colon; Colorectal cancer; Derivatives; Kinases; NMR; Nuclear magnetic resonance; Selectivity; Tyrosine
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c9ra03359a

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. A new series of phenylaminopyrimidine (PAP) derivatives was designed and synthesized to act against tyrosine kinases for the treatment of cancer.