Novel thiazole derivatives: Design, synthesis, antibacterial evaluation, DFT, molecular docking and in-silico ADMET investigations

Thiazole derivatives (7a-f and 9a-i) were synthesized in good yields (up to 98%). The synthetic protocol is achieved through a two-step reaction. The synthesized candidates were then evaluated for their antimicrobial efficacies against gram-positive and gram-negative bacteria. 4-methyl-2-(2-(3-(pentyloxy)benzylidene)hydrazinyl)-5-(p-tolyldiazenyl)thiazole showed significant antimicrobial activity against Staphylococcus aureus (ATCC: 13565) compared to ampicillin. On the other hand, 2-(2-(3-(hexyloxy)benzylidene)hydrazinyl)-4-(4-methoxyphenyl)thiazole shows potent activity against Klebsiella pneumonia (ATCC: 10031) compared to gentamicin as a standard antibiotic. The ADME profile of the prepared compounds indicated favorable pharmacological behaviors. Additionally, docking and in-silico ADMET analyses were performed for the promising derivatives and the results revealed strong antimicrobial activity. DFT calculations were performed, which provided additional insight into the thiazoles’ structure and formation.