Click chemistry assisted synthesis of imidazo[1,2-a]pyrimidine-1,2,3-triazole hybrids as promising antitubercular agents: Design, characterization, in-vitro biological evaluation, molecular docking, DFT and in-silico ADME studies

Abstract

In this work, the molecular hybridization approach was employed to design a series of imidazo[1,2-a]pyrimidine -1,2,3-triazole derivatives (P1-P18), and the designed hybrid molecules were synthesized using a click chemistry protocol. The structure of one of the final compounds P10, was validated by single-crystal X-ray diffraction investigation. Among these 18 compounds, P3, P13, and P15 demonstrated encouraging antitubercular action against the M. tuberculosis H37Rv strain with minimum inhibitory concentrations (MIC) of 12.05 and 11.95 µM of (P3 and P13) or 6.75 µM (P15). In addition, at various concentrations, the target compounds demonstrated strong antifungal activity against P. anomala and A. flavus and antibacterial activity against S. aureus and Escherichia coli. The potent anti-TB agents (P3, P13, and P15) are non-toxic in the toxicity test performed using VERO cell lines. Furthermore, In-silico ADME, molecular docking (with InhA and CYP121), and DFT analysis data revealed that the active compounds have substantial potential as candidates for the development of novel antitubercular medicines. © 2025 Elsevier B.V.