Synthesis, computational studies and evaluation of benzisoxazole tethered 1,2,4-triazoles as anticancer and antimicrobial agents

A novel series of six compounds, benzisoxazole tethered 1,2,4-triazoles were synthesized in five steps with good yields and characterized. ¹H NMR, ¹³C NMR and mass spectrometry confirmed the formation of the derivatives. Antimicrobial activity was evaluated for the synthesized derivatives against three bacterial strains (Escherichia coli, Mycobacterium smegmatis and Staphylococcus aureus) and a fungal strain (Candida albicans). Similarly, anticancer activity was assessed against MCF-7 cell lines. The biological analysis disclosed that, out of the six compounds, derivative 6c showed better antimicrobial and anticancer activity with MIC of 12.5 μg/mL against Staphylococcus aureus and Mycobacterium smegmatis; and IC₅₀ of 35.57 μM against MCF-7 cancer cell line. Theoretical evaluation provides an insight about ligand interaction with proteins, highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), electronegativity, hardness, softness, electrophilicity and neucleophilicity of the ligands via molecular docking and density functional theory (DFT) studies; this presents probable evidence for the biological activity of the derivatives. Molecular Dynamics (MD) simulation of the ligand 6c with protein HDAC7 (PDB ID: 3ZNR) was studied.