New tetrahydrobenzo[b]thiophene-1,2,4-triazole hybrids: Synthesis, antimicrobial activity, and computational investigation
TL;DR
The emphasized docking score results obtained for 5e, 5f, and 5i proved the major impact of these derivatives on the interacting residues of the receptor (PDB ID: 1M17) as well as density functional theory and molecular docking analysis.
Abstract
The present study explored the synthesis of ten new molecules embedded with 1,2,4-triazole scaffolds (5a-5j), followed by in vitro biological screening along with in silico computational investigations, including density functional theory (DFT) and molecular docking analysis. The target hybrids (5a-5j) were synthesized through sequential esterification, hydrazide formation, cyclization to the 1,2,4-triazole-5-thiol intermediate, and subsequent S-alkylation with substituted benzyl halides. Out of all the new hybrids (5a-5j), compounds 5e, 5f, and 5i disclosed noteworthy activity against all six subjected microorganisms, together with both bacterial and fungal species. DFT analysis was adopted for the three selected motifs (5e, 5f, and 5i), encompassing highest occupied molecular orbital-lowest unoccupied molecular orbital evaluation, global reactivity descriptors, and molecular electrostatic potential mapping. Epidermal growth factor receptor tyrosine kinase (Protein data bank [PDB] ID: 1M17) was chosen as the preferred model receptor for the computational docking studies since it has been subjected to many ligand-protein interaction experiments. The emphasized docking score results obtained for 5e, 5f, and 5i proved the major impact of these derivatives on the interacting residues of the receptor (PDB ID: 1M17).. KEYWORDS :1,2,4-Triazole, Antimicrobial activity, Density functional theory, Molecular docking.