Antikinetoplastid Activity of Indolocarbazoles from Streptomyces sanyensis

Biomolecules

卷:10

JoséJ. Fernández¹  Luis Cartuche¹  AnaR. Díaz-Marrero¹  Ines Sifaoui²  Atteneri López-Arencibia²  Desirée San Nicolás-Hernández²  JoséE. Piñero²  CarlosJ. Bethencourt-Estrella²  Jacob Lorenzo-Morales² 

[1] Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Tenerife, Spain;

[2] Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, Spain;

关键词: Indolocarbazole;    kinetoplastid;    Streptomyces;    leishmanicidal;    trypanocidal;   

DOI  :  10.3390/biom10040657

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown