Synthesis, molecular docking, and antimicrobial activity of novel scaffolds based on bis(thiazole) linked to 2-phenoxy-N-arylacetamide as new hybrid molecules

The reaction of the appropriate bis(alpha-haloketones) with the corresponding thiosemicarbazones in EtOH at reflux in the presence of a few drops of TEA produced good yields of novel bis-thiazoles linked to 2-phenoxy-N-arylacetamide as novel hybrid molecules. The isomeric bis(thiazoles) were prepared under similar reaction conditions by reacting the appropriate bis(thiosemicarbazone) with the corresponding alpha-haloketones. All of the newly synthesized compounds were tested against four bacterial strains. Compounds 8g and 8i have the most antibacterial activity against S. aureus and Bacillus subtilis. The molecular docking studies supported our findings, which demonstrated that compounds 8g and 8i could fit with favorable binding energies in the active sites of bacterial DNA gyrase B and thymidylate kinase, respectively.