Dedicated to Prof. Carsten Bolm for his significant contributions in the area of mechanochemical organic synthesis.Chemical structures possessing both 1,2,3-triazole and bis(indolyl)methane fragments gained considerable interest in drug synthesis owing to their established biological efficacies. However, 1,2,3-triazoles linked at the bridging position of bis(indolyl)methane is a logical and unexplored design approach. In this regard, nine new triazolyl-bis(indolyl)methane conjugates under AuCl catalyzed ball-milling conditions were accomplished. Comparative evaluation on absorptive and emissive properties of the synthesized dyads were also analyzed. To unravel the influence of different peripheral substituents on the electronic structure and π-orbital properties, theoretical investigations were performed. Screening of molecules for free radical scavenging, anti-inflammatory and antidiabetic showed comparable potency against reference drugs. In particular, compounds 7 h, 7 d and 7 a displayed good efficiency of α-amylase inhibition. The DNA gyrase inhibitory potential of all compounds were assessed in silico which revealed high binding affinity (ΔG = À 8.99 Kcal/mol) for 7 i followed by 7 h (ΔG = À 7.80 Kcal/mol) with the targeted protein.
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.
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