Desai Nisheeth C, Satodiya Hitesh M, Kotadiya Ghanshyam M, Vaghani Hasit V
Division of Medicinal Chemistry, Department of Chemistry, Mahatma Gandhi Campus, Maharaja Krishnakumarsinhji Bhavnagar University, Bhavnagar, Gujarat, India.
Arch Pharm (Weinheim). 2014 Jul;347(7):523-32. doi: 10.1002/ardp.201300466. Epub 2014 Apr 14.
Two new series of N-3 substituted thiazolidine-2,4-dione derivatives bearing the pyrazole moiety (5a-j and 7a-j) were synthesized and assessed in vitro for their efficacy as antibacterial agents against gram-positive and gram-negative bacterial strains. Among the tested compounds, 7b, 7c, 7i, and 7j were found to be active against gram-positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) with minimum inhibitory concentration (MIC) values in the range of 6.25-25 µg/mL, and some compounds were also tested against methicillin-resistant S. aureus (MRSA). Compounds 7c and 7j inhibited the growth of MRSA at MIC values of 6.25 and 12.5 µg/mL, respectively. The influence of the lipophilicity (C log P) on the biological profile (MIC) of the prepared products was also discussed. From the standpoint of structure-activity relationship studies, it was observed that the lipophilic profiles of the compounds were crucial for their antibacterial activities. Further, the results of the MTT cytotoxicity studies on a human cervical cancer cell line (HeLa) and a mouse embryonic fibroblast cell line (NIH 3T3) suggested that compounds 7b, 7c, 7i, and 7j were endowed with low levels of cytotoxicity.
合成了两个带有吡唑部分的新型N-3取代噻唑烷-2,4-二酮衍生物系列（5a-j和7a-j），并在体外评估了它们作为抗革兰氏阳性和革兰氏阴性细菌菌株的抗菌剂的功效。在测试的化合物中，发现7b、7c、7i和7j对革兰氏阳性细菌（金黄色葡萄球菌和化脓性链球菌）具有活性，最低抑菌浓度（MIC）值在6.25-25μg/mL范围内，并且一些化合物还针对耐甲氧西林金黄色葡萄球菌（MRSA）进行了测试。化合物7c和7j分别在MIC值为6.25和12.5μg/mL时抑制了MRSA的生长。还讨论了亲脂性（C log P）对所制备产物的生物学特性（MIC）的影响。从构效关系研究的角度来看，观察到化合物的亲脂性概况对其抗菌活性至关重要。此外，对人宫颈癌细胞系（HeLa）和小鼠胚胎成纤维细胞系（NIH 3T3）进行的MTT细胞毒性研究结果表明，化合物7b、7c、7i和7j具有低水平的细胞毒性。
