Eco-friendly synthesis of novel functionalized thiazolidine heterocycles and evaluation of its antimicrobial activity

Abstract

The ongoing prevalence of multidrug-resistant microbial pathogens requires the development of new effective antimicrobial agents. In the modern scenario, thiazolidine scaffold has emerged as a very potent scaffold as per its clinicalsignificance concerned. Past fewyears, various newer synthetic approaches have been designed to synthesize diverse scaffolds to explorethe various types of biological activities. In our study,a new series of 2,2 phenylmethyl-3-thioureido-5-arylidene thiazolidine-4-one derivatives have been synthesized with acetophenone, thiosemicarbazide and mercaptoacetic acid in absolute ethanol in one pot manner in presence of zinc chloride catalyst followed by aldol condensation using ammonium chloride and substituted aldehydes in green fashion technique. The striking features of the reaction are the formation of new thiosemicarbazone in situ which in turn undergoes cyclization with mercaptoacetic acid, leading to the formation of Thioureido-thiazolidinones as a precursor. Next, the precursors undergo eco-friendly aldol condensation in the presence of ammonium chloride. The new compounds were characterized by spectroscopic evidence. Among all the synthesized novel thiazolidine-4-one derivatives,2,2-phenylmehyl-3-thioureido-5-benzylidene thiazolidine-4-one, 2,2-phenylmethyl-3-thioureido-5-(p-(N, N-dimethyl amino) benzylidene) thiazolidine-4-one, 2,2-(p-Bromo phenyl)methyl-3-thioureido-5-benzylidene thiazolidine-4-one and 2,2-(p-Bromo phenyl)methyl-3-thioureido-5-(p-(N, N-dimethyl amino) benzylidene) thiazolidine-4-one were evaluated for their antimicrobial activityagainst five gram-positive bacteria (Bacillius sereus, Bacillius megaterium, Bacillius subtilis, Staphylococcus aureus, Sarcina lutea), eight gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphi, Salmonella typhi, Shigella boydii, Shigella dysenteriae, Vibrio mimicus, Vibrio parahemolyticus) and three fungi (Candida albicans, Aspergillus niger, Sacharomyces cerevacae). Biological screening of the tested compounds revealed that an extra arylidene group with the precursor beside carbonyl group can affect the activity against microbes. Our research work shows that using green techniques, it is possible toincrease the antimicrobial activity of the precursor by introducing extra arylidene substituent.