Aims This study aims to design and synthesize a new series of hybrid heterocyclic systems and to evaluate their anticancer and antimicrobial properties. Additionally, in silico analyses were performed to assess their molecular interactions, pharmacokinetic profiles, and potential as drug candidates.Materials & methods The compounds were synthesized via a 3 + 2 cycloaddition reaction. Biological evaluations included in vitro cytotoxicity assays against four human cancer cell lines. Antibacterial activity was assessed against representative Gram-positive and Gram-negative strains. In silico studies encompassed molecular docking with bacterial protein targets, molecular dynamics simulations, and ADMET profiling.Results The synthesized compounds (5–6) were successfully characterized and demonstrated moderate antiproliferative activity against cancer cell lines. Compound 6 showed slightly higher cytotoxicity than compound 5, with an IC50 of 17.16 ± 2.43 µM against A549. Both compounds exhibited notable antibacterial activity, particularly against Gram-negative strains. Docking studies revealed favorable binding energies at the active sites of selected bacterial proteins, while MD simulations confirmed the stability of ligand-protein complexes.Conclusions This work demonstrates the successful synthesis and biological evaluation of novel isoxazole-based heterocyclic hybrids. Compound 6 emerged as the most promising candidate, exhibiting moderate anticancer activity, significant antibacterial effects, and strong in silico evidence of stable TLR4 inhibition.
Al‐Saleem et al. (Fri,) studied this question.