噻唑烷酮衍生物新型骨架的抗弓形虫活性的合成及生物学评价

Carradori Simone, Secci Daniela, Bizzarri Bruna, Chimenti Paola, De Monte Celeste, Guglielmi Paolo, Campestre Cristina, Rivanera Daniela, Bordón Claudia, Jones-Brando Lorraine

a Department of Pharmacy , "G. D'Annunzio" University of Chieti-Pescara , Chieti , Italy.

b Department of Drug Chemistry and Technologies , Sapienza University of Rome , Rome , Italy.

J Enzyme Inhib Med Chem. 2017 Dec;32(1):746-758. doi: 10.1080/14756366.2017.1316494.

We designed and synthesised novel N-substituted 1,3-thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii efficacy. This scaffold was functionalised both at the N1-hydrazine portion with three structurally different moieties and at the lactam nitrogen with substituted benzyl groups selected on the basis of our previous structure-activity relationships studies. Using three different assay methods, the compounds were assessed in vitro to determine both the levels of efficacy against the tachyzoites of T. gondii (IC = 5-148 μM), as well as any evidence of cytotoxicity towards human host cells (TD = 68 to ≥320 μM). Results revealed that ferrocene-based thiazolidinones can possess potent anti-tachyzoite activity (TI =2-64).

我们设计并合成了新型N-取代的1,3-噻唑烷-4-酮衍生物，以评估其抗刚地弓形虫的功效。该骨架在N1-肼部分用三个结构不同的基团进行功能化修饰，在内酰胺氮上用基于我们之前的构效关系研究选择的取代苄基进行修饰。使用三种不同的测定方法，对这些化合物进行体外评估，以确定其对刚地弓形虫速殖子的功效水平（IC = 5-148 μM），以及对人类宿主细胞的任何细胞毒性证据（TD = 68至≥320 μM）。结果表明，基于二茂铁的噻唑烷酮具有有效的抗速殖子活性（TI = 2-64）。