KOR

e-Article

Chromatin regulation in schistosomes and histone modifying enzymes as drug targets
Document Type
article
Source
Memorias do Instituto Oswaldo Cruz, Vol 106, Iss 7, Pp 794-801 (2011)
Subject
Schistosoma mansoni
histone modifying enzyme
histone deacetylase
inhibitor
drug target
Microbiology
QR1-502
Infectious and parasitic diseases
RC109-216
Language
English
ISSN
1678-8060
0074-0276
Abstract
Only one drug is currently available for the treatment and control of schistosomiasis and the increasing risk of selecting strains of schistosome that are resistant to praziquantel means that the development of new drugs is urgent. With this objective we have chosen to target the enzymes modifying histones and in particular the histone acetyltransferases and histone deacetylases (HDAC). Inhibitors of HDACs (HDACi) are under intense study as potential anti-cancer drugs and act via the induction of cell cycle arrest and/or apoptosis. Schistosomes like other parasites can be considered as similar to tumours in that they maintain an intense metabolic activity and rate of cell division that is outside the control of the host. We have shown that HDACi can induce apoptosis and death of schistosomes maintained in culture and have set up a consortium (Schistosome Epigenetics: Targets, Regulation, New Drugs) funded by the European Commission with the aim of developing inhibitors specific for schistosome histone modifying enzymes as novel lead compounds for drug development.