In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of New Arylamine Mannich Base-Type Derivatives
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- 作者：Elsa Moreno-ViguriCarmen Jiménez-Montes ; Rubén Martín-Escolano ; Mery Santivañez-Veliz ; Alvaro Martin-Montes ; Amaya Azqueta ; Marina Jimenez-Lopez ; Salvador Zamora Ledesma ; Nuria Cirauqui ; Adela López de Ceráin ; Clotilde Marín ; Manuel Sánchez-Moreno ; Silvia Pérez-Silanes
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：December 22, 2016
- 年：2016
- 卷：59
- 期：24
- 页码：10929-10945
- 全文大小：802K
- ISSN：1520-4804
文摘
Chagas disease is a neglected tropical disease with 6–7 million people infected worldwide, and there is no effective treatment. Therefore, there is an urgent need to continue researching in order to discover novel therapeutic alternatives. We present a series of arylaminoketone derivatives as means of identifying new drugs to treat Chagas disease in the acute phase with greater activity, less toxicity, and a larger spectrum of action than that corresponding to the reference drug benznidazole. Indexes of high selectivity found in vitro formed the basis for later in vivo assays in BALB/c mice. Murine model results show that compounds 3, 4, 7, and 10 induced a remarkable decrease in parasitemia levels in acute phase and the parasitemia reactivation following immunosuppression, and curative rates were higher than with benznidazole. These high antiparasitic activities encourage us to propose these compounds as promising molecules for developing an easy to synthesize anti-Chagas agent.