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2020-08-21
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NO-DONOR DIHYDROARTEMISININ DERIVATIVES AS MULTITARGET AGENTS FOR THE TREATMENT OF CEREBRAL MALARIA
Bertinaria, Massimo et al. | Date Issued: 2015
Author
Bertinaria, Massimo
Orjuela-Sanchez, Pamela
Marini, Elisabetta
Guglielmo, Stefano
Hofer, Anthony
Martins, Yuri C.
Zanini, Graziela M.
Frangos, John A.
Gasco, Alberto
Fruttero, Roberta
Carvalho, Leonardo J. M.
Affilliation
Università degli Studi di Torino. Dipartimento di Scienza e Tecnologia del Farmaco. Torino, Italy.
La Jolla Bioengineering Institute. La Jolla, CA, USA.
Università degli Studi di Torino. Dipartimento di Scienza e Tecnologia del Farmaco. Torino, Italy.
Università degli Studi di Torino. Dipartimento di Scienza e Tecnologia del Farmaco. Torino, Italy.
La Jolla Bioengineering Institute. La Jolla, CA, USA.
La Jolla Bioengineering Institute. La Jolla, CA, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia. Laboratório de Parasitologia. Rio de Janeiro, RJ, Brasil.
La Jolla Bioengineering Institute. La Jolla, CA, USA.
Università degli Studi di Torino. Dipartimento di Scienza e Tecnologia del Farmaco. Torino, Italy.
Università degli Studi di Torino. Dipartimento di Scienza e Tecnologia del Farmaco. Torino, Italy.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.
Abstract
Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized and studied as potential tools for the treatment of cerebral malaria (CM). The designed products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA, comparable to artesunate and artemether. Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6% compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral malaria.
Keywords
Malaria
Cerebral Malaria
Treatment
 
Publisher
American Chemical Society
Citation
BERTINARIA, Massimo et al. NO-donor dihydroartemisinin derivatives as multitarget agents for the treatment of cerebral malaria. Journal of Medicinal Chemistry, v. 58, n. 19, p. 7895-7899, Oct. 2015.
DOI
10.1021/acs.jmedchem.5b01036
ISSN
0022-2623