Desiatkina Oksana, Păunescu Emilia, Mösching Martin, Anghel Nicoleta, Boubaker Ghalia, Amdouni Yosra, Hemphill Andrew, Furrer Julien
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012, Bern, Switzerland.
Institute of Parasitology Vetsuisse Faculty, University of Bern, Länggass-Strasse 122, 3012, Bern, Switzerland.
Chembiochem. 2020 Oct 1;21(19):2818-2835. doi: 10.1002/cbic.202000174. Epub 2020 Jun 16.
The synthesis, characterization, photophysical and biological properties of 13 new conjugate coumarin-diruthenium(II)⋅arene complexes against Toxoplasma gondii are presented. For all conjugate organometallic unit/coumarins, an almost complete loss of fluorescence efficacy was observed. However, the nature of the fluorophore, the type of bonding, the presence and length of a linker between the coumarin dye and the ruthenium(II) moiety, and the number of dye units influenced their biological properties. The in vitro activity against a transgenic T. gondii strain grown in human foreskin fibroblasts (HFF) leads to IC values for T. gondii β-gal from 105 to 735 nM. Of note is that nine compounds displayed lower IC than the standard drug pyrimethamine. One compound applied at its IC did not affect B-cell proliferation but had an impact on T-cell proliferation in murine splenocyte cultures. Transmission electron microscopy of T. gondii β-gal-infected HFF showed that treatment predominantly affected the parasites' mitochondrion.
本文介绍了13种新型共轭香豆素-二钌（II）⋅芳烃配合物对刚地弓形虫的合成、表征、光物理和生物学性质。对于所有共轭有机金属单元/香豆素，观察到荧光效率几乎完全丧失。然而，荧光团的性质、键合类型、香豆素染料与钌（II）部分之间连接基的存在和长度以及染料单元的数量影响了它们的生物学性质。对在人包皮成纤维细胞（HFF）中生长的转基因刚地弓形虫菌株的体外活性导致刚地弓形虫β-半乳糖苷酶的IC值为105至735 nM。值得注意的是，九种化合物的IC值低于标准药物乙胺嘧啶。一种化合物在其IC值下应用不影响B细胞增殖，但对小鼠脾细胞培养中的T细胞增殖有影响。对刚地弓形虫β-半乳糖苷酶感染的HFF进行透射电子显微镜检查表明，治疗主要影响寄生虫的线粒体。
