Synthesis of novel S-acyl and S-alkylpyrimidinone derivatives as potential cytotoxic agents

Two series of 4-phenyl-5-cyanopyrimidin-6-one derivatives bearing various S-alkyl or S-acyl moieties at position 2 were prepared as cytotoxic agents. All compounds were tested for possible anti-cancer activity on two cell lines (MCF-7 and HCT-116). The MCF-7 cell line was found to be more sensitive than the HCT-116 cell line to the action of the compounds. Compound 8g was the most potent on the MCF-7 cell line with IC50 18.3 nM/mL, whereas its IC50 on the normal cell line (MRC-5) was 64.38 nM/mL, indicating its safety and selectivity towards the MCF-7 cell line. On the other hand, compound 8d was the most potent compound on the HCT-116 cell line with IC50 23.8 nM/mL. Compound 8g was screened against five kinases. The compound showed selective inhibitory activity against pim1 kinase with IC50 11.62 mu M. [GRAPHICS] .