Synthesis, computational studies of new thymol derived chalcones and their benzotriazoles as antimicrobial agents

The ineffectiveness of antimicrobial agents, efforts have been made to synthesize new thymol derived chalcones to treat microbial infections effectively. Molecular docking, computational properties and antimicrobial evaluation were performed for newly synthesized chalcones. A series of new chalcones as potential antimicrobial agents (7T 1 -7T 7 and 9T 1 -9T 3 ) were characterized by FTIR, 1 H NMR, 13 C NMR and HRMS spectral techniques. Molecular docking, ligand-receptor complex binding energies, ADMET, drug-likeness properties and similarity were assessed for test compounds by software programs. Chalcones were synthesized by the reaction of thymol with 1-bromo-3-chloropropane and then treated with aminoacetophenone and benzaldehydes. Benzotriazole analogs (9T 1 , 9T 2 and 9T 3 ) were further synthesized by reaction of 3-(2-chlorophenyl)−1-(4-(3-(2-isopropyl-5-methylphenoxy) propyl) amino) phenyl) prop-2-en-1-one (7T 1 ) with 1H-benzo[ d ] [1,2,3] triazole. The results of computational properties were good for test compounds as compared with standard drugs. The docking study indicated strong binding of compounds (7T1 and 9T2) with DNA gyrase (−6.08 Kcal/mol) and lanosterol (−11.10 kcal/mol). Test compounds were evaluated for antimicrobial activity against S. aureus , E. coli, C. albicans , and C. mycoderma using the broth dilution method with standard drugs amoxicillin, norfloxacin, and fluconazole. The potency of 7T 1 against E. coli (MIC 13.5 µg/ml) and 7T 2 against S. aureus (MIC 12.16 µg/ml) was remarkable. 9T 1 and 9T 2 showed good potency against C. albicans and C. mycoderma (MIC of 12.91 and 14.72 µg/ml, respectively). The designed thymol-derived chalcone offers an exciting scaffold for exploration as an antimicrobial agent. Nevertheless, more experimental support is required for the pathways that pharmacological studies have proposed. Design of new antimicrobial chalcones.