| Author | Vasconcelos, Eveline Gomes | |
| Author | Resende, Dayse Moura | |
| Author | Vianello, Marco Aurélio | |
| Author | Bordin, Fábio Humberto da Silveira | |
| Author | Jacinto, Alexandre Arthur | |
| Author | Dias, Walkyria Dutra | |
| Author | Montesano, Maria Ângela | |
| Author | Nelson, David Lee | |
| Author | Coelho, Paulo Marcos Zech | |
| Author | Vasconcelos, Eveline Gomes | |
| Access date | 2023-07-28T19:42:46Z | |
| Available date | 2023-07-28T19:42:46Z | |
| Document date | 2007 | |
| Citation | PENIDO, Marcus Luiz Oliveira et al. A new series of schistosomicide drugs, the alkylaminoalkanethiosulfuric acids, partially inhibit the activity of Schistosoma mansoni ATP diphosphohydrolase. European Journal of Pharmacology, v. 570, n. 1–3, p. 10-17, 2007. doi.org/10.1016/j.ejphar.2007.05.028 | en_US |
| ISSN | 1879-0712 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/59837 | |
| Language | eng | en_US |
| Publisher | Elsevier B.V. | en_US |
| Rights | restricted access | |
| Title | A new series of schistosomicide drugs, the alkylaminoalkanethiosulfuric acids, partially inhibit the activity of Schistosoma mansoni ATP diphosphohydrolase | en_US |
| Type | Article | |
| DOI | 10.1016/j.ejphar.2007.05.028 | |
| Abstract | The effects of the alkylammoalkanethiosulfuric acids (AAATs), new schistosomicidal drugs, on Schistosoma mansoni ATP diphosphohydrolase isoforms, members of the NTPDase family, were analyzed. Pre-incubation of worm adult tegument with AAATs derivatives, with small apolar alkyl groups and an apolar alkane portion of 6 or 8 carbon atoms linked to the amino group, inhibited ATPase activity with a Ki 100-1000 mu M. Little inhibition (20%) was observed when ADP was the substrate. The 2-[(tert-butyl)amino]-1-ethinethiosulfuric acid (100 mu M) which has a less lipophilic structure, inhibited 28% ATPase and 12% ADPase activities, suggesting that the lipophilicity, although important, is not the only requisite for enzyme activity inhibition. The N-(sec-butyl)-2-bromo-1-octanaminium bromide, which contains a bromide atom instead of thiosulphate, inhibited < 10% of the enzyme activity, suggesting the involvement of cysteine residue(s) from S. mansoni ATP diphosphohydrolase isoforms in a mixed disulfide formation. Treatment of parasite tegument with 5 mM iodoacetamide or 1 mM dithiothreitol protected ATPase and ADPase activities against inhibition by AAATs, corroborating the participation of disulfide interchange in the AAATs mechanism. Since S. mansoni ATP diphosphohydrolase isoforms and potato apyrase share structural similarities, the latter enzyme was also tested. ADPase activity from potato apyrase was inhibited by 55%, showing a higher sensitivity to I mM AAATs than that shown by ADPase activity from the tegument, while the ATPase activities from both samples showed similar inhibition levels. Furthermore, sulfhydryl reagents protected potato apyrase activity. Therefore, it is possible that both soluble S. mansoni ATP diphosphohydrolase and membrane-associated isoforms are targets for the AAATs. | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Alimentos. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Santa Casa de Misericórdia de Belo Horizonte. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Juiz de Fora. Instituto de Ciências Biológicas. Departamento de Bioquímica. Juiz de Fora, MG, Brazil | en_US |
| Subject | ATP diphosphohydrolase | en_US |
| Subject | NTPDase | en_US |
| Subject | schistosoma mansoni | en_US |
| Subject | potato apyrase | en_US |
| Subject | alkylaminoalkanethiosulfuric acids | en_US |
| Embargo date | 2099-12-31 | |
