Secci Daniela, Carradori Simone, Bizzarri Bruna, Chimenti Paola, De Monte Celeste, Mollica Adriano, Rivanera Daniela, Zicari Alessandra, Mari Emanuela, Zengin Gokhan, Aktumsek Abdurrahman
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Department of Pharmacy, "G. D'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Eur J Med Chem. 2016 Jul 19;117:144-56. doi: 10.1016/j.ejmech.2016.04.012. Epub 2016 Apr 8.
Pursuing our recent outcomes regarding the antifungal activity of N-substituted 1,3-thiazolidin-4-ones, we synthesized thirty-six new derivatives introducing aliphatic, cycloaliphatic and heteroaromatic moieties at N1-hydrazine connected with C2 position of the thiazolidinone nucleus and functionalizing the lactam nitrogen with differently substituted (NO2, NH2, Cl and F) benzyl groups. These compounds were tested to evaluate their minimum inhibitory concentration (MIC) against several clinical Candida spp. with respect to topical and systemic reference drugs (clotrimazole, fluconazole, ketoconazole, miconazole, tioconazole, amphotericin B). Moreover, anti-oxidant properties were also evaluated by using different protocols including free radical scavenging (DPPH and ABTS), reducing power (CUPRAC and FRAP), metal chelating and phosphomolybdenum assays. Moreover, for the most active derivatives we assessed the toxicity (CC50) against Hep2 human cells in order to characterize them as multi-target agents for fungal infections.
基于我们最近关于N-取代的1,3-噻唑烷-4-酮抗真菌活性的研究成果,我们合成了36种新衍生物,在与噻唑烷酮核C2位相连的N1-肼基上引入脂肪族、脂环族和杂芳族部分,并使用不同取代(NO2、NH2、Cl和F)的苄基对内酰胺氮进行官能化。针对局部和全身参考药物(克霉唑、氟康唑、酮康唑、咪康唑、噻康唑、两性霉素B),测试了这些化合物对几种临床念珠菌属的最小抑菌浓度(MIC)。此外,还通过不同方案评估了抗氧化性能,包括自由基清除(DPPH和ABTS)、还原能力(CUPRAC和FRAP)、金属螯合和磷钼酸测定。此外,对于活性最高的衍生物,我们评估了其对Hep2人细胞的毒性(CC50),以便将它们表征为真菌感染的多靶点药物。