Synthesis of novel bioactive pyrido[2,3-d]pyrimidine derivatives with potent cytotoxicity through apoptosis as PIM-1 kinase inhibitors.

ABSTRACT: Direct synthesis and cytotoxicity activity of new series of pyrido[2,3-d]pyrimidine was described. Nicotinamide 2 was synthesized via cyclization of N-cyclohexyl derivative with cyanoacetamide. The o-aminonicotinonitrile 2 was subjected to acylation or thio acylation process followed by intramolecular heterocyclization to afford the desired pyrido[2,3-d]pyrimidine (3-10) and pyrido triazine 11. Compounds 4 and 11 exhibited remarkable cytotoxicity against MCF-7 cells with IC₅₀ values of 0.57 μM and 1.31 μM and IC₅₀ values of 1.13 μM and 0.99 μM against HepG2 cells. Interestingly, compounds 4 and 10 had potent PIM-1 kinase inhibition with IC₅₀ values of 11.4 and 17.2 nM, respectively, with inhibition of 97.8% and 94.6% compa

SUBMITTER: Tantawy ES 

PROVIDER: S-EPMC10996840 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature