Antiamoebic Activities of Indolocarbazole Metabolites Isolated from <i>Streptomyces sanyensis</i> Cultures

• Main Authors: Luis Cartuche, María Reyes-Batlle, Ines Sifaoui, Iñigo Arberas-Jiménez, José E. Piñero, José J. Fernández, Jacob Lorenzo-Morales, Ana R. Díaz-Marrero
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Marine Drugs
• Subjects: indolocarbazole; staurosporine; <i>streptomyces sanyensis</i>; antiparasitic activities; <i>acanthamoeba</i>
• Online Access: https://www.mdpi.com/1660-3397/17/10/588

Indolocarbazoles are a family of natural alkaloids characterized by their potent protein kinase and topoisomerase I inhibitory activity. Among them, staurosporine (<b>1</b>) has exhibited promising inhibitory activity against parasites. Based on new insights on the activity and mechanism of action of STS in <i>Acanthamoeba</i> parasites, this work reports the isolation, identification, and the anti-<i>Acanthamoeba</i> activity of the minor metabolites 7-oxostaurosporine (<b>2</b>), 4&#8242;-demethylamino-4&#8242;-oxostaurosporine (<b>3</b>), and streptocarbazole B (<b>4</b>), isolated from cultures of the mangrove strain <i>Streptomyces sanyensis.</i> A clear correlation between the antiparasitic activities and the structural elements and conformations of the indolocarbazoles <b>1</b>&#8722;<b>4</b> was observed. Also, the study reveals that 7-oxostaurosporine (<b>2</b>) affects membrane permeability and causes mitochondrial damages on trophozoites of <i>A. castellanii</i> Neff.