| Registro completo |
| Provedor de dados: |
ArchiMer
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| País: |
France
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| Título: |
Alkoxyamines Designed as Potential Drugs against Plasmodium and Schistosoma Parasites
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| Autores: |
Reyser, Thibaud
To, Tung H.
Egwu, Chinedu
Paloque, Lucie
Nguyen, Michel
Hamouy, Alexandre
Stigliani, Jean-luc
Bijani, Christian
Augereau, Jean-michel
Joly, Jean-patrick
Portela, Julien
Havot, Jeffrey
Marque, Sylvain R. A.
Boissier, Jérôme
Robert, Anne
Benoit-vical, Françoise
Audran, Gérard
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| Data: |
2020-09
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| Ano: |
2020
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| Palavras-chave: |
Alkoxyamine
Alkylation
Heme
Malaria
Radical chemistry
Schistosomiasis
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| Resumo: |
Malaria and schistosomiasis are major infectious causes of morbidity and mortality in the tropical and sub-tropical areas. Due to the widespread drug resistance of the parasites, the availability of new efficient and affordable drugs for these endemic pathologies is now a critical public health issue. In this study, we report the design, the synthesis and the preliminary biological evaluation of a series of alkoxyamine derivatives as potential drugs against Plasmodium and Schistosoma parasites. The compounds (RS/SR)-2F, (RR/SS)-2F, and 8F, having IC50 values in nanomolar range against drug-resistant P. falciparum strains, but also five other alkoxyamines, inducing the death of all adult worms of S. mansoni in only 1 h, can be considered as interesting chemical starting points of the series for improvement of the activity, and further structure activity, relationship studies. Moreover, investigation of the mode of action and the rate constants kd for C-ON bond homolysis of new alkoxyamines is reported, showing a possible alkyl radical mediated biological activity. A theoretical chemistry study allowed us to design new structures of alkoxyamines in order to improve the selectivity index of these drugs
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| Tipo: |
Text
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| Idioma: |
Inglês
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| Identificador: |
https://archimer.ifremer.fr/doc/00648/76024/76920.pdf
https://archimer.ifremer.fr/doc/00648/76024/76921.pdf
DOI:10.3390/molecules25173838
https://archimer.ifremer.fr/doc/00648/76024/
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| Editor: |
MDPI AG
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| Formato: |
application/pdf
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| Fonte: |
Molecules (1420-3049) (MDPI AG), 2020-09 , Vol. 25 , N. 17 , P. 3838 (23p.)
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| Direitos: |
info:eu-repo/semantics/openAccess
restricted use
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