title: Trypanosoma cruzi: evaluation of (-)-cubebin derivatives activity in the messenger RNAs processing.
abstract: No fully effective treatment has been developed since the discovery of Chagas' disease. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effective in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing, which is unusual RNA processing reaction, and it implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. Cubebin derivatives seem to provide treatments with less collateral effects than benznidazole and showed similar or better trypanocidal activities than benznidazole. Therefore, the cubebin derivatives ((-)-6,6'-dinitrohinokinin (DNH) and (-)-hinokinin (HQ)) interference in the mRNA processing was evaluated using T. cruzi permeable cells (Y and BOL (Bolivia) strains) following by RNase protection reaction. These substances seem to intervene in any step of the RNA transcription, promoting alterations in the RNA synthesis, even though the RNA processing mechanism still occurs. Furthermore, HQ presented better activity against the parasites than DNH, meaning that BOL strain seems to be more resistant than Y.
authors.affiliation: Grupo de Pesquisas em Produtos Naturais, Núcleo de Pesquisas em Ciências Exatas e Tecnológicas da Universidade de Franca, 14404-600 Franca, São Paulo, Brazil. mlasilva@unifran.br
authors.forename: Márcio Luís
authors.initials: ML
authors.lastname: Andrade e Silva
authors.forename: Regina Maria Barretto
authors.initials: RM
authors.lastname: Cicarelli
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Pauletti
authors.forename: Priscilla Paiva
authors.initials: PP
authors.lastname: Luz
authors.forename: Karen Cristina Souza
authors.initials: KC
authors.lastname: Rezende
authors.forename: Ana Helena
authors.initials: AH
authors.lastname: Januário
authors.forename: Rosangela
authors.initials: R
authors.lastname: da Silva
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Pereira
authors.forename: Jairo Kenupp
authors.initials: JK
authors.lastname: Bastos
authors.forename: Sérgio
authors.initials: S
authors.lastname: de Albuquerque
authors.forename: Lizandra Guidi
authors.initials: LG
authors.lastname: Magalhães
authors.forename: Wilson Roberto
authors.initials: WR
authors.lastname: Cunha
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017705:Lignans / Q000138:chemical synthesis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D020040:Trans-Splicing / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D017705:Lignans; D012333:RNA, Messenger; C433065:cubebin