Novel pyrimidine Schiff bases and their selenium-containing nanoparticles as dual inhibitors of CDK1 and tubulin polymerase: design, synthesis, anti-proliferative evaluation, and molecular modelling.

Nanotechnology-based strategies can overcome the limitations of conventional cancer therapies. Hence, novel series of pyrimidine Schiff bases () were employed in the synthesis of selenium nanoparticle forms (). All selenium nano-sized forms exerted greater inhibitions than normal-sized compounds, far exceeding 5-fluorouracil activity. Compound showed effective anti-proliferative activity against MCF-7(IC 3.14 ± 0.04 µM), HepG-2(IC 1.07 ± 0.03 µM), and A549(IC 1.53 ± 0.01 µM) cell lines, while its selenium nanoform showed excellent inhibitory effects, with efficacy increased by 96.52%, 96.45%, and 93.86%, respectively. Additionally, outperformed in selectivity against the Vero cell line by 4.5-fold. Furthermore, exhibited strong inhibition of CDK1(IC 0.47 ± 0.3 µM) and tubulin polymerase(IC 0.61 ± 0.04 µM), outperforming and being comparable to roscovitine (IC 0.27 ± 0.03 µM) and combretastatin-A4(IC 0.25 ± 0.01 µM), respectively. Moreover, both and arrested the cell cycle at G0/G1 phase and significantly forced the cells towards apoptosis. Molecular docking demonstrated that and were able to inhibit CDK1 and tubulin polymerase binding sites.