Puttachari, D.Naik, S.Veeranagaiah, N.S.Udayakumar, U.2026-02-032025ChemistrySelect, 2025, 10, 31, pp. -https://doi.org/10.1002/slct.202501537https://idr.nitk.ac.in/handle/123456789/20121In this study, a molecular hybridization strategy was used to design a series of imidazo[1,2-a]pyrimidine-linked pyridine, pyrazine, and pyrimidine derivatives (T1–T20) and the hybrid compounds were synthesized via a multistep procedure. The structure of one of the target compounds T11, was studied using single-crystal X-ray diffraction investigation. These final molecules were thoroughly tested against Mycobacterium tuberculosis H37Rv strain, and compound T11 showed the best activity with MIC of 0.8 µg/mL, while compounds T5 and T18 showed promising inhibition activity (MIC 3.12 µg/mL). The target compounds were further tested for antibacterial activity against Staphylococcus aureus and Escherichia coli, finding the MIC and MBC values. Many of the compounds exhibited notable antibacterial properties. The promising anti-TB drugs (T5, T11, and T18) were shown to be nontoxic in toxicity studies on VERO cell lines. The combined results from in silico ADME, molecular docking, and DFT studies indicate that the active compounds possess strong potential as antitubercular candidates. © 2025 Wiley-VCH GmbH.Antibacterial activityCytotoxicityIn silico studiesMolecular dockingMycobacterium tuberculosisPyrazinePyrimidine