A nanodelivered Vorinostat derivative is a promising oral compound for the treatment of visceral leishmaniasis

Publication date: Available online 29 November 2018Source: Pharmacological ResearchAuthor(s): Victoriano Corpas-López, Mónica Díaz-Gavilán, Francisco Franco-Montalbán, Gemma Merino-Espinosa, Margarita López-Viota, Julián López-Viota, Efres Belmonte-Reche, José Pérez-del Palacio, Nuria de Pedro, José Antonio Gómez-Vidal, Francisco Morillas-Márquez, Joaquina Martín-SánchezAbstractThere is currently no satisfactory treatment for visceral leishmaniasis; the disease is thus in desperate need of novel drugs. The ideal candidate should be effective, safe, affordable, and administered via the oral route. Histone deacetylases (HDACs) are involved in silencing critical regulatory pathways, including pro-apoptotic programs, and represent potential therapeutic targets for pharmacological interventions. O-alkyl hydroxamates have traditionally been considered to exert no effect on mammal HDACs. The aim of this study was to evaluate the effect of MDG, a SAHA derivative of the O-alkyl hydroxamate family with no activity on human histone deacetylase enzymes, on the visceral leishmaniasis causative agents and in a murine model of the disease. The effects of vorinostat, tubacin and valproic acid (well-known mammal HDAC inhibitors) on the parasite were also evaluated. MDG was found to be highly active against Leishmania infantum and L. donovani intracellular amastigotes in vitro but not against the promastigote stage. In contrast, vorinostat, tubacin and valproic acid showed no ac...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research