噻唑烷-4-酮衍生物作为有前景的弓形虫抑制剂的设计、合成及生物学特性研究
Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii.
作者信息
D'Ascenzio Melissa, Bizzarri Bruna, De Monte Celeste, Carradori Simone, Bolasco Adriana, Secci Daniela, Rivanera Daniela, Faulhaber Nathan, Bordón Claudia, Jones-Brando Lorraine
机构信息
Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
出版信息
Eur J Med Chem. 2014 Oct 30;86:17-30. doi: 10.1016/j.ejmech.2014.08.046. Epub 2014 Aug 15.
We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition.
我们设计并合成了大量新型噻唑烷-4-酮衍生物，以评估它们的抗弓形虫活性。该骨架在N1-肼部分用脂肪族、脂环族和（杂）芳族部分进行了官能化。然后，在核心核的内酰胺NH处引入苄基侧链，以评估这种化学修饰对生物活性的影响。对这些化合物进行了多种体外试验，以评估它们的抗寄生虫功效、对成纤维细胞的细胞毒性、对速殖子侵袭/附着的抑制作用以及处理后的复制情况。结果表明，这些基于噻唑的化合物中有14种在抑制寄生虫生长方面与对照化合物甲氧苄啶相当。
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