Design, synthesis, and biological evaluation of 2-butyl-4-chloroimidazole-derived 1,3,4-oxadiazoles: ACE inhibition, anticancer, and antitubercular activities

• Design of 2-Butyl-4-Chloroimidazole-Derived 1,3,4-Oxadiazoles • Synthesis and Characterization of 2-Butyl-4-Chloroimidazole-Derived 1,3,4-Oxadiazoles • ACE Inhibition, Anticancer, and Antitubercular Activities • Molecular docking, ADME, and Simulation studies • Study of Structure-activity relationships A novel series of eight compounds , 2-butyl-4-chloroimidazole-derived 1,3,4-oxadiazoles, were designed and synthesized conveniently over four steps in good yield. The synthesized 1,3,4-oxadiazoles were confirmed via various analytical techniques, such as FTIR, 1 H NMR, 13 C NMR, and mass spectrometry. The ACE enzyme inhibitory potential of the synthesized compounds was evaluated, with compounds 5b and 5c showing IC 50 values of 81.29 ± 0.70 and 51.01± 1.58 µM, respectively. Additionally, the synthesized compounds were screened for anticancer activity against the MDA-MB-231 and Caco-2 cell lines, and an antitubercular evaluation against the M. tuberculosis H37RV strain was also carried out. In silico studies, such as molecular docking to determine orientation and binding interactions, ADME prediction to determine Lipinski's rule, and molecular dynamics simulations to evaluate ligand‒protein stability were also conducted.