Modular and Computational Access to Innocuous Multistep Metal-Free Synthesis of 1,3,4-Oxadiazoles as Enzyme Inhibitors.

An array of 1,3,4-oxadiazole hybrids, , structurally intriguing cores with potential in natural product synthesis and drug discovery, have been synthesized using innovative comparable conventional and microwave-assisted protocols. The synthesis was performed by the reaction of secondary amine-based acetamides, , as the electrophile and piperidine-based oxadiazoles as the nucleophile, , under the metal-free reaction conditions. High yield in minimum time with highest purity was obtained by the microwave-irradiated method instead of the conventional one. The structural elucidations were made through infrared, H NMR, C NMR, and elemental analysis studies. The whole array of synthesized compounds, , was evaluated for their potential against α-glucosidase and butyryl cholinesterase (BChE) enzymes. Natural bond orbital and structural optimizations were made by using the B3LYP method and the basis set of 6-311++G(d,p). Frontier molecular orbitals and molecular electrostatic potential were calculated at the same level of selected compounds as potential candidates against BChE and α-glucosidase enzymes utilizing the time-dependent density functional theory. Fifteen compounds out of 19 were observed to be active against α-glucosidase enzyme in comparison with acarbose as the reference standard and 7 against the BChE enzyme compared to eserine as the reference standard. The highest potential of compound against BChE is well correlated by the higher binding interaction with target protein as -10.2, calculated by docking studies. The recruited compounds against both enzymes could be the best anti-enzymatic drugs and part of drugs discovery programs after further analysis.