in silico molecular docking, scaffold hopping, and pass prediction of designed pyrimidine-based analogues their synthesis and biological evaluation

A series of pyrimidine derivatives was synthesized using an environ-mentally friendly biginelli reaction, where benzaldehyde analogs, ethyl acetoacetate, and urea were condensed under alkaline conditions. mo-lecular docking against cyclin-dependent kinase (cdk, pdb id: 1hck) revealed docking scores ranging from –5.8 to –8.7, compared to –5.3 for ascorbic acid. among these, compound 2g exhibited the most favorable binding (–8.7), suggesting strong potential for further investigation. scaffold-hopping analysis using the mcule 1-click-scaffold-hop server generated structural analogs, and pass prediction indicated diverse biological activities. specific compounds displayed enhanced activity predictions: compounds 2b, 2e, and 2f showed moderate anti-inflammatory potential (pa = 0.588), 2m demonstrated higher anti-inflammatory (pa = 0.620) and nadh kinase inhibitory activity (pa = 0.582), while 2d showed notable kinase inhibitory (pa = 0.653) and an-tioxidant (pa = 0.566) potential. the synthesized compounds exhibited concentration-dependent radical scavenging activity in the range of 100–500 ppm. at 100 ppm, compound 2a achieved the highest scaveng-ing rate (89.84%), surpassing ascorbic acid (77.12%). these results val-idate the in silico prediction of antioxidant properties. in antimicrobial screening, streptomycin was ineffective against e. coli and streptococ-cus spp. in contrast, compound 2d displayed significant antibacterial activity, supporting its selection for further biological evaluation.