Multi‐Technique Investigation of Pyrimidine‐2‐thione Azo Dyes as AKT Signaling Inhibitors: Synthesis, NCI, ELF, LOL, Molecular Docking, and ADMET Studies

ABSTRACT The reaction of pyrimidine 2‐thione ( 1 ) with 3,5‐diamino‐1,2,4‐triazole produced Schiff base ( 2) . New azo compounds ( 3‐7) are produced when the diazonium salt of compound 2 reacts with different imidazole and pyrazolone derivatives. Numerous spectroscopic techniques were used to elucidate the structure of the synthesized compounds. Following this, the pharmacokinetic properties and in silico evaluation of the azo derivatives to inhibit the active form of the AKT protein were studied. Additionally, the anticancer properties were tested in vitro against different cancer cell lines. Compound 5 exhibited the best anticancer activity, with IC50 values of 15.81 ± 1.1 µM against HepG‐2 and 18.08 ± 1.3 µM against MCF‐7, respectively. Additionally, compound 5 demonstrated a strong capacity to scavenge DPPH free radicals. DFT was also employed to investigate the molecular structures of compounds 3–7 using the 6‐311G(d) basis set. The LUMO, HOMO, and MEP were measured to understand the reactive sites of the molecules. The Pauli repulsion effect was examined through the application of the LOL and ELF methodologies. NCI emphasized the subtle interactions. This study uses an integrated experimental and computational strategy to identify a novel pyrimidine‐2‐thione azo scaffold that targets the AKT signaling pathway.