PROFILING THE HDAC INHIBITORS ACTIVITY AGAINST THE MODEL OF CESTODE PARASITES Mesocestoides corti

VACA, HUGO R.; CELENTANO, ANA M.; MACCHIAROLI, N.; CAMICIA, F.; ROSENZVIT, MARA C.

Mar del Plata, Provincia de Buenos Aires

Congreso; Reunión Conjunta SAIC SAI SAFIS 2019; 2019

Sociedad Argentina de investigacion clinica (SAIC)

Echinococcosis and cysticercosis areneglected diseases (1) caused by the cestode parasites Echinococcus ssp. and Taenia solium, respectively. These diseases affect socioeconomically disadvantaged population and represent a significant problem in human and animal health.There is a scarce availability of compounds approved for chemotherapy. Thus, it is imperative to identify new drugs. In this work, we investigated histone deacetylase (HDAC) enzymes as potential drug targets to develop new therapies against neglected diseases caused by cestodes. We previously reported the presence and expression of HDACs in several cestode parasites. Furthermore, we showed that Trichostatin A (TSA), a pan-HDAC inhibitor, produces a decrease in parasite viability, alterations on the tegument and morphology and an increment of the total amount of acetylated proteins, including acetylated histone H4, on the cestode laboratory model Mesocestoides corti (2). Here, we present the activity profile of a series of HDAC- inhibitors (HDACi) against on viability of M. corti larvae, using a worm tracker device for high-throughput screening in parallel with microscopy observation. We evaluated 40 compounds, comprising HDACi against class I, II and III HDACs. The commercial compounds Entinostat (a HDACi against class I HDACs) and Mz25 (a HDACi against class III HDACs), and two structure-based novel inhibitors designed against the HDAC8 from Schistosoma mansoni (3) were the most potent HDACi. These compounds produced a decrease of 100% in the viability and alterations on the tegument and morphology of M. corti at concentrations of 20 and 50 μM (p