Design and Synthesis of New Aryloxy‐linked Dimeric 1,2,3‐Triazoles via Click Chemistry Approach: Biological Evaluation and Molecular Docking Study

Abstract

A quest for more potent new antitubercular agents has prompted to design and synthesize aryloxy‐linked dimeric 1,2,3‐triazoles (4a–j), from azides (2a‐e) and bis(prop‐2‐yn‐1‐yloxy)benzene (3a–b) on 1,3‐dipolar cycloaddition reaction via copper (I)‐catalyzed click chemistry approach with good to better yields. The titled compounds (4a–j) were designed using molecular hybridization approach by assembling various bioactive pharmacophoric fragments in a single molecular framework. All the synthesized compounds have been screened for their in vitro antitubercular, antifungal, and antioxidant activities against their respective strains. Among them, 4h and 4i show the highest antifungal activity, whereas compounds 4h, 4i, and 4j have revealed promising antitubercular activity against their respective strains. In addition to this, most of the synthesized compounds were found as potent antifungal and antioxidant agents. A significant network of bonded and non‐bonded interactions stabilized these molecules into the active site of fungal CYP51 that is realized from the obtained well‐placed docking poses and the associated thermodynamic interactions with the enzyme. The synthesized compounds have also been analyzed for absorption, distribution, metabolism, and excretion properties.