Alkoxyamines Designed as Potential Drugs against Plasmodium and Schistosoma Parasites.

Autor:	Reyser T; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France., To TH; Aix Marseille University, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille CEDEX 20, France., Egwu C; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France., Paloque L; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France., Nguyen M; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France., Hamouy A; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France., Stigliani JL; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France., Bijani C; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France., Augereau JM; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France., Joly JP; Aix Marseille University, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille CEDEX 20, France., Portela J; S.A.S ParaDev, 52 Avenue Paul Alduy, 66860 Perpignan, France., Havot J; Aix Marseille University, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille CEDEX 20, France., Marque SRA; Aix Marseille University, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille CEDEX 20, France., Boissier J; Laboratoire Interactions Hôtes-Pathogènes-Environnements (IHPE), UMR 5244 CNRS, University of Perpignan, IFREMER, Univ. Montpellier, F-66860 Perpignan, France., Robert A; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France., Benoit-Vical F; Laboratoire de Chimie de Coordination du CNRS, LCC-CNRS, Université de Toulouse, CNRS, 31555 Toulouse, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France.; INSERM, Institut National de la Santé et de la Recherche Médicale, 31024 Toulouse, France., Audran G; Aix Marseille University, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille CEDEX 20, France.
Jazyk:	angličtina
Zdroj:	Molecules (Basel, Switzerland) [Molecules] 2020 Aug 24; Vol. 25 (17). Date of Electronic Publication: 2020 Aug 24.
DOI:	10.3390/molecules25173838
Abstrakt:	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 IC 50 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 k d 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.
Databáze:	MEDLINE
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