A New 1,2,3-Triazole-Based Benzooxepines: Design, Synthesis, and In Silico Docking, ADME-T and Antimicrobial Evaluation

In this work, the molecular hybridization approach was employed to design a series of benzooxepine linked to 1,2,3-triazolyl chalcone structures, and the prepared molecules were synthesized using a click chemistry protocol. Several spectral approaches, including infrared, ¹H NMR, ¹³C NMR, IR and HRMS spectrometric analysis, were used to determine the product structures. Three of the investigated compounds p-fluorophenyl, and o-nitrophenyl substituted chalcones shown remarkable antibacterial susceptibilities against the tested strain of S. aureus, with MICs (minimum inhibitory concentrations) ranging from 4.26±0.52 to 6.19±0.11 μg/mL. When compared to clotrimazole (MIC = 6.10±0.81 μg/mL), the prepared scaffolds showed better antifungal activity against C. albicans, with MIC values ranging from 4.45±0.14 to 38.79±1.32 μg/mL. Furthermore, a small number of derivatives with MIC ranges of 3.01 to 5.12 μM showed comparable antitubercular activity against the H₃₇Rv strain. Docking experiments verified one of the ligand abilities to build a stable compound on the CYP51 active site from M. TB (PDB code: 1EA1). The chalcone-1,2,3-triazole hybrids molecular properties, bioactivity scores, toxicity assessment, and ADME were also evaluated. Furthermore, In-silico ADME, molecular docking revealed that the active compounds have substantial potential as candidates for the development of novel antitubercular medicines.