Design, synthesis, and computational studies as cytotoxicity of novel pyrimidine carbonitrile derivatives as dual-target inhibitors of BRD4.

Structural-based drug design was employed to create new pyrimidine carbonitrile compounds for dual BRD4. The compounds were identified using IR, 1H-NMR, 13C-NMR, and mass spectra. The compounds fit the volasertib binding site at BRD4 and exhibit drug-like characteristics and pharmacokinetics, making them potential anticancer candidates. All of the compounds interacted with the highest number of targets. Compound 1 had the greatest interactions, engaging with four anticancer targets (5V67, 3FC2, 3IG7, and 4ASD). Compare the ADME study results for compounds 1–3 to those for volasertib. Overall, all of the rule principles that might indicate drug-likeness for the tested compounds 1, 2, and 3 performed admirably, suggesting that these substances may fulfill the cell membrane permeability and bioavailability criteria. All 3 targets associated with anti-cancer illness were docked separately with each medication. These compounds have extraordinarily high binding affinities for all 3 anticancer targets. Compounds 1, 2, and 3 showed similar interactions to Volasertib when docked into BRD4 active sites. These compounds also demonstrated superior drug-likeness and pharmacokinetics compared to Volasertib itself.