In Vitro and in Vivo Trypanocidal Evaluation of Nickel Complexes with an Azapurine Derivative against Trypanosoma cruzi
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- 作者：Carmen R. Maldonado ; Clotilde Marn ; Francisco Olmo ; Oscar Huertas ; Miguel Quirs ; Manuel Snchez-Moreno ; Mara J. Rosales ; Juan M. Salas
- 刊名：Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：October 14, 2010
- 年：2010
- 卷：53
- 期：19
- 页码：6964-6972
- 全文大小：1019K
- 年卷期：v.53,no.19(October 14, 2010)
- ISSN：1520-4804
文摘
Seven ternary nickel(II) complexes (three previously described and four firstly described here) with an azapurine derivative (the anionic form of 4,6-dimethyl-1,2,3-triazolo[4,5-d]pyrimidin-5,7-dione) have been synthesized and spectroscopically characterized, and the crystal structures of three of them have been solved by X-ray diffraction. Studies in vitro and in vivo on the antiproliferative activity of these complexes against Trypanosoma cruzi (epimastigote, amastigote, and trypomastigote forms) have been carried out, displaying in some cases significantly higher antitrypanosomatid activity and lower toxicity than the reference drug for Chagas’ disease, benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide). Ultrastructural analysis and metabolism excretion studies were also executed in order to propose a possible mechanism of action for the assayed drugs.