Biological features, drug-likeness, pharmacokinetic properties, and docking of 2-arylidenehydrazinyl-4-arylthiazole analogues

Thiazoles are an important class of heterocyclic compounds that possess a sulfur and nitrogen containing five-membered ring, which acts as a pharmacophore, and show a wide range of complex biological activities. A series of sixteen 2-arylidenehydrazinyl-4-arylthiazole analogues ( 3a – p ) were evaluated for cytotoxic activity against brine shrimp ( Artemia salina ) nauplii and their minimum inhibitory concentrations were determined against two Gram-positive ( Listeria monocytogenes and Enterococcus faecalis ) and two Gram-negative bacterial strains ( C. sakazakii and E . coli ). Of the tested compounds, 3g demonstrated highest cytotoxicity with a LC 50 value of 54 ppm followed by compound 3h ( LC 50 = 85 ppm), in a short-term bioassay using A. salina , whereas compound 3i exhibited the most potent antibacterial activities against L. monocytogenes , E. faecalis , and C. sakazakii with MIC values ranging from 50 to 100 μg mL −1 . Compound 3g showed highest antibacterial activity against E. coli (MIC = 50 μg mL −1 ). In silico drug-likeness, pharmacokinetic (ADME) properties, toxicity effects, and drug scores were also evaluated, and none of the sixteen compounds were found to violate Lipiniski’s rule of five or Veber’s rule, indicating potential for development as oral drug candidates. In addition, a docking study of compound 3i into the active site of E. coli FabH receptor, an attractive target for the development of new antibacterial agents, showed it has good binding properties.