Synthesis and In Vitro Screening of Some New Thiazolone-based Schiff Bases as Potential MurB Inhibitors

Abstract: MurB is an enzyme that is crucial to the survival of bacterial strains. Recently, considerable interest has been generated in developing new antibacterial agents that effectively inhibit MurB. We synthesized herein new thiazolone-based Schiff bases derived from salicylaldehydes in good yields. The appropriate thiosemicarbazones were prepared and then reacted with a variety of hydrazonyl chlorides in dioxane. The reaction was mediated using an equimolar amount of triethylamine. The new Schiff bases were tested against six different ATCC bacterial strains with the reference ciprofloxacin. Generally, Schiff bases 2a-2f linked to 5-((4- chlorophenyl)thio)methyl units outperformed their analogues 1a-1f linked to 5-(phenylthio)methyl units fourfold. The best activity was obtained from Schiff base 2f linked to the 5-(2-(4- methoxyphenyl)hydrazineyl)thiazol-4(5H)-one unit. Product 2f had more effective antibacterial activity than ciprofloxacin, with MIC/MBC of 1.8/3.7 µM against S. aureus and E. faecalis. It also exhibited good activity against S. mutans and K. pneumoniae, with MIC/MBC values of 3.7/7.4 µM. Moreover, 2e exhibited the second- highest activity against all tested strains, with MIC/MBC values of 3.8/7.6 µM for S. aureus and E. faecalis, and 7.6/15.3 µM for S. mutans and K. pneumoniae. Schiff bases with potential antibacterial activity were further screened for their MurB inhibitory activity. Furthermore, 2e and 2f displayed the best inhibitory activity against MurB with IC50 of 5.0 and 4.6 µM, respectively. conclusion: Generally, Schiff bases linked to 5-((4-chlorophenyl)thio)methyl units outperformed their analogues linked to 5-(phenyl)thio)methyl units fourfold in the antibacterial activity. Moreover, adding an electron-releasing unit into the aryldiazenyl unit increased activity.