Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi

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• 作者：Minni Pirttimaa ; Abedelmajeed Nasereddin ; Dmitry Kopelyanskiy ; Marcel Kaiser ; Jari Yli-Kauhaluoma ; Kirsi-Marja Oksman-Caldentey ; Reto Brun ; Charles L. Jaffe ; Vânia M. Moreira ; Sami Alakurtti
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：February 26, 2016
• 年：2016
• 卷：79
• 期：2
• 页码：362-368
• 全文大小：321K
• ISSN：1520-6025

文摘

Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC₅₀ value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC₅₀ value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC₅₀ value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.