Design, synthesis, in silico studies and antiproliferative evaluation of some novel hybrids of pyrimidine-morpholine

It was demonstrated that all derivatives had appropriate cytotoxic potential with IC₅₀ in range of 5.12-117.04 μM. Compound <b>2g</b> was identified as the most potent compound, exhibiting IC₅₀ values of 5.10 ± 2.12 μM and 19.60 ± 1.13 μM toward the SW480 and MCF-7 cell lines, respectively. Cell cycle analysis showed that <b>2g</b> could induces phase arrest in MCF-7 breast cancer cells. The apoptosis assay demonstrated the induction of apoptosis in the SW480 cell line. The biological activity of the compounds was confirmed by the docking studies. DFT analysis for compounds <b>2g</b> and <b>2h</b> was conducted at the B3LYP/6-31+G** level of theory. It was concluded that <b>2g</b> is both thermodynamically and kinetically more stable than <b>2h</b>. Moreover, the interpretation of ADME (Absorption, Distribution, Metabolism, and Excretion) indicates that these new series of compounds possess acceptable prognostic physicochemical properties. These synthesized compounds may serve as promising candidates for further investigation as anticancer agents.