Targeting schistosome histone modifying enzymes for drug development

dc.creatorPierce, Raymond John
dc.creatorAbdesselem, Florence Dubois
dc.creatorLancelot, Julien
dc.creatorMacedo, Luiza Freire de Andrade e
dc.creatorOliveira, Guilherme Correa de
dc.date2015-08-12T18:14:47Z
dc.date2015-08-12T18:14:47Z
dc.date2012
dc.date.accessioned2023-09-26T22:23:06Z
dc.date.available2023-09-26T22:23:06Z
dc.identifierPIERCE, Raymond John et al. Targeting schistosome histone modifying enzymes for drug development. Current Pharmaceutical Design, vol.18, n. 24, p. 3567-3578, 2012.
dc.identifier1381-6128
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11442
dc.identifier10.2174/138161212801327248
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8878557
dc.descriptionThe histone modifying enzymes (HME) represent particularly promising targets for the development of alternatives to praziquantel, the only currently available drug to combat schistosomiasis. The inhibition of these enzymes frequently arrests the cell cycle or induces apoptosis in cancer cells, but not in normal cells and numerous HME inhibitors are under investigation as potential anticancer agents. The recent resolution of the genome sequences of Schistosoma mansoni and Schistosoma japonicum has allowed us to identify all the schistosome genes encoding histone acetyltransferases, deacetylases, methyltransferases and demethylases. We have chosen a strategy using phylogenetic screening with inhibitors of HME classes, screening of individual HME targets by both high-throughput and reasoned (in silico docking using resolved crystal structures) approaches in a project funded by the European Community, named SEtTReND (Schistosome Epigenetics: Targets, Regulation, New Drugs). The initial focus is on the class I histone deacetylase (HDAC) 8 since the comparison of the catalytic site of the schistosome and human enzymes shows crucial differences, rendering possible the development of inhibitors specific for SmHDAC8. However, phenotypic screening shows that inhibitors of all HME classes tested were able to induce apoptosis and death in parasites in vitro, indicating that other enzymes may prove to be viable targets.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBentham Science Publishers
dc.rightsrestricted access
dc.subjectSchistosoma mansoni
dc.subjecthistone modifying enzyme
dc.subjecthistone deacetylase
dc.subjectinhibitor
dc.subjectdrug target
dc.subjectpraziquantel
dc.subjectapoptosis
dc.subjectschistosome genes
dc.subjectSEtTReND
dc.subjectSmHDAC8
dc.titleTargeting schistosome histone modifying enzymes for drug development
dc.typeArticle


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