Synthesis, computer‐aided ADMET prediction, and molecular docking of novel 3,5,6‐trichloropyridin‐2‐yl derivatives as potential antimicrobial agents

Abstract

Abstract3,5,6‐Trichloropyridin‐2‐yl derivatives were synthesized and tested for antimicrobial activity. The chemical structures were inferred from the correct accurate spectroscopic and analytical data of the 1H‐NMR, 13C‐NMR, and MS techniques. The compounds were examined and screened for their in vitro antibacterial activity against Bacillus cereus (G+), Staphylococcus aureus (G+), Escherichia coli (G−), and Pseudomonas aeruginosa (G−). In addition, the compounds were evaluated as candidacidal agents against Candida albicans. Compounds 5, 7, and 8 were superior against bacteria to the standard. In both in vitro experiments and in silico studies, these compounds proved to be the most effective against bacteria and candida. A number of parameters relating to the physicochemical properties, drug‐likeness, and ADMET parameters have been simulated. Lipinski's parameter assessment showed that the synthesized compounds had good permeability in biological membranes and good gastrointestinal absorption (Log S of −4.06 to −5.77 and PSA <140). Molecular docking to the active sites of penicillin‐binding protein 2a (PDB: 1VQQ), and lanosterol 14‐alpha demethylase (PDB 1EA1), as target proteins, revealed that most compounds displayed minimal binding energy and have a good affinity toward the active pocket of each enzyme. This is the first article to describe the antimicrobial properties of 3,5,6‐trichloropyridin‐2‐yl‐based molecules derivatives.