Step-Economical Mechanosynthesis of Hybrid Azoles: Deciphering Their π-Orbital and Pharmacological Characteristics

A hybrid pharmacophore strategy for unifying 1,2,3-triazole with 1,2,4-triazole cores to prepare mixed triazoles was accomplished by a ball-milling approach. The developed chemistry works under the catalysis of cupric oxide nanoparticles with salient features like one-jar operation, lower number of synthetic steps, catalyst recyclability, time-dependent product control, and good overall yields. π-Orbital properties based on theoretical calculations supported the suitability of these molecules for pharmacological screening. Therefore, the biological potency of the synthesized molecules was evaluated for antioxidant, anti-inflammatory, and anti-diabetic activities. By virtue of their proton-donating tendency, all compounds showed promising radical-scavenging activity with the inhibition level reaching up to 90 %. These molecular hybrids also exhibited anti-inflammatory and anti-diabetic potencies similar to those of standard compounds, owing to their electron-rich nature. Finally, α-amylase inhibitory potential was demonstrated in silico; significant regions necessary for enzyme inhibition were identified by hydrogen bonding interactions.