Synthesis, Computer-Aided Admet Prediction, and Molecular Docking of Novel 3,5,6-Trichloropyridin-2-Yl Derivatives as Potential Antimicrobial Agents

A series of 3,5,6-trichloropyridin-2-yl based molecules (1-8) with different active moieties have been designed, synthesized and tested for antibacterial and candidacidal 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. Among the newly synthesized molecules, compounds 5, 7, and 8 successfully inhibited all the tested microorganisms and 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. They thus would serve as a promising lead for potential antimicrobial compounds. A number of parameters relating to the physicochemical properties, drug-likeness, and ADMET parameters have been simulated. Based on Lipinski's parameter assessment, 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.