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.

journal_name

Parasitol Res

journal_title

Parasitology research

authors

Andrade e Silva ML,Cicarelli RM,Pauletti PM,Luz PP,Rezende KC,Januário AH,da Silva R,Pereira AC,Bastos JK,de Albuquerque S,Magalhães LG,Cunha WR

doi

10.1007/s00436-011-2275-x

subject

Has Abstract

pub_date

2011-08-01 00:00:00

pages

445-51

issue

2

eissn

0932-0113

issn

1432-1955

journal_volume

109

pub_type

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