title: NO-Donor Dihydroartemisinin Derivatives as Multitarget Agents for the Treatment of Cerebral Malaria.
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.
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino , Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bertinaria
authors.affiliation: La Jolla Bioengineering Institute , 505 Coast Boulevard South, Suite 411, La Jolla, California 92037, United States.
authors.forename: Pamela
authors.initials: P
authors.lastname: Orjuela-Sanchez
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino , Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marini
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino , Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guglielmo
authors.affiliation: La Jolla Bioengineering Institute , 505 Coast Boulevard South, Suite 411, La Jolla, California 92037, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Hofer
authors.affiliation: La Jolla Bioengineering Institute , 505 Coast Boulevard South, Suite 411, La Jolla, California 92037, United States.
authors.forename: Yuri C
authors.initials: YC
authors.lastname: Martins
authors.affiliation: Laboratório de Parasitologia, Instituto Nacional de Infectologia, Fiocruz, Rio de Janeiro, 21040-360, Brazil.
authors.forename: Graziela M
authors.initials: GM
authors.lastname: Zanini
authors.affiliation: La Jolla Bioengineering Institute , 505 Coast Boulevard South, Suite 411, La Jolla, California 92037, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Frangos
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino , Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
authors.affiliation: Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino , Via P. Giuria 9, 10125 Torino, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.affiliation: Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, 21040-900, Brazil.
authors.forename: Leonardo J M
authors.initials: LJ
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology; D000077332:Artesunate; D060326:Chemistry Techniques, Synthetic; D016779:Malaria, Cerebral / Q000188:drug therapy*; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009126:Muscle Relaxation / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000494:pharmacology*; D010962:Plasmodium berghei / Q000187:drug effects; D051381:Rats; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D000077332:Artesunate; C039060:artenimol; D000077549:Artemether