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Antikinetoplastid Activity of Indolocarbazoles from Streptomyces sanyensis

2020; Multidisciplinary Digital Publishing Institute; Volume: 10; Issue: 4 Linguagem: Inglês

10.3390/biom10040657

2218-273X

Luis Cartuche, Inés Sifaoui, Atteneri López‐Arencibia, Carlos J. Bethencourt-Estrella, Desirée San Nicolás-Hernández, Jacob Lorenzo‐Morales, José E. Piñero, Ana R. Díaz‐Marrero, José J. Fernández,

Phytochemical compounds biological activities

Chagas disease and leishmaniasis are neglected tropical diseases caused by kinetoplastid parasites of Trypanosoma and Leishmania genera that affect poor and remote populations in developing countries. These parasites share similar complex life cycles and modes of infection. It has been demonstrated that the particular group of phosphorylating enzymes, protein kinases (PKs), are essential for the infective mechanisms and for parasite survival. The natural indolocarbazole staurosporine (STS, 1) has been extensively used as a PKC inhibitor and its antiparasitic effects described. In this research, we analyze the antikinetoplastid activities of three indolocarbazole (ICZs) alkaloids of the family of staurosporine STS, 2-4, and the commercial ICZs rebeccamycin (5), K252a (6), K252b (7), K252c (8), and arcyriaflavin A (9) in order to establish a plausive approach to the mode of action and to provide a preliminary qualitative structure-activity analysis. The most active compound was 7-oxostaurosporine (7OSTS, 2) that showed IC50 values of 3.58 ± 1.10; 0.56 ± 0.06 and 1.58 ± 0.52 µM against L. amazonensis; L. donovani and T. cruzi, and a Selectivity Index (CC50/IC50) of 52 against amastigotes of L. amazonensis compared to the J774A.1 cell line of mouse macrophages.