Synthesis, characterization, anti-lung cancer activity, and in-silico studies of some novel triazole-based analogues as Pellizzari products

In the present research work, a series of novel (Z)-5-(cyclohexylidenehydrazono)-2-aryl-3H,5H-thiazolo[3,4-b] [1,2,4]triazole derivatives were synthesized by Pellizzari reaction of (Z)-3-amino-2-(cyclo hexylidenehydrazono) thiazolidin-4-one with different aromatic amides. All the synthesized products were obtained in a good to excellent yields, and their structures were established based on UV-Vis, FT-IR, 1H NMR, 13C NMR, and HRMS analysis. To validate the experimental findings, in-silico studies of one synthesized compound (11a) were done with the help of density functional theory (DFT) at B3LYP/6-311++G(d,p) level. Frontier molecular orbitals, molecular electrostatic potential, and Reduced density gradient analysis were performed to better understand the electronic properties, and reactivity. Results of NLO, ELF, LOL, DOS, AIM, and vector analysis were reported. All the newly synthesized benzimidazole compounds had a cytotoxic impact, in some cases much more potent than the reference medication. The cytotoxicity of all the synthesized compounds were assessed against A549 cell lines using the MTT assay. Among them, compounds 11d and 11e showed more potent cytotoxicity having the IC50 value -90 and -80 mu M, respectively. The molecular docking studies revealed an excellent affinity for the active sites of the matching gene regulation -inhibitor complex (BDR4) protein. Additionally, the evaluation of ADMET parameters indicated good pharmacokinetic properties of all the investigated compounds.