Synthesis, structure and structure–activity relationship analysis of 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives as potential antibacterial agents

Nine 2-arylthiazolidine-4-carboxylic acid derivatives and nine 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives were synthesized to screen for their antibacterial activities. Compounds 5, 14–18 were first reported. Their chemical structures were clearly determined by 1H NMR, 13C NMR, ESI mass spectra and elemental analyses, coupled with one selected single-crystal structure. All the compounds were assayed for antibacterial activities against two Gram-positive bacterial strains (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacterial strains (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) by MTT method. Most of the 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives exhibited better antibacterial activities against the four bacterial strains than relative 2-arylthiazolidine-4-carboxylic acid derivatives. Compound (2RS,4R)-3-(tert-butoxycarbonyl)-2-(5-fluoro-2-hydroxyphenyl)thiazolidine-4-carboxylic acid (14) showed powerful antibacterial activities against P. aeruginosa with IC50 value of 0.195 μg/mL, which was superior to the positive controls Penicillin G and Kanamycin B, respectively. On the basis of the biological results, structure–activity relationships were discussed.

Graphical abstractThe newly synthesized (2RS,4R)-3-(tert-butoxycarbonyl)-2-(5-fluoro-2-hydroxyphenyl) thiazolidine-4-carboxylic acid (14) exhibited higher selective antibacterial activities against pathogenic bacterium Pseudomonas aeruginosa with IC50 value of 0.195 μg/mL than positive controls Kanamycin G and Penicillin B did respectively. The crystal structure of (2R,4R)-3-(tert-butoxycarbonyl)-2-(4-methoxyphenyl)thiazolidine-4-carboxylic acid was also first reported.Figure optionsDownload full-size imageDownload as PowerPoint slide