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 (1)H NMR, (13)C 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 IC(50) value of 0.195 microg/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.
Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Zhong-Cheng
ZC
Song
Gao-Yuan
GY
Ma
Peng-Cheng
PC
Lv
Huan-Qiu
HQ
Li
Zhu-Ping
ZP
Xiao
Hai-Liang
HL
Zhu
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D018360:Crystallography, X-Ray; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D053778:Thiazolidines; C003438:thiazolidine-4-carboxylic acid