new 1-aryl-3-substituted propanol derivatives as antimalarial agents新1-aryl-3-substituted丙醇衍生物的抗疟药物.pdfVIP

Molecules 2009, 14, 4120-4135; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article New 1-Aryl-3-Substituted Propanol Derivatives as Antimalarial Agents Silvia Pérez-Silanes 1,*, Luis Berrade 1, Rory N. García–Sánchez 2, Adela Mendoza 1, 1 2 2 Silvia Galiano , Berta Martín Pérez-Solórzano , Juan J. Nogal-Ruiz , Antonio R. Martínez-Fernández 2, Ignacio Aldana 1 and Antonio Monge 1 1 Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), University of Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain; E-Mail: luisberrade@ (L.B.) 2 Departamento de Parasitología, Facultad de Farmacia, Complutense University of Madrid, Spain * Author to whom correspondence should be addressed; E-Mail: sperez@unav.es. Received: 11 August 2009; in revised form: 21 September 2009 / Accepted: 14 October 2009 / Published: 14 October 2009 Abstract: This paper describes the synthesis and in vitro antimalarial activity against a P. falciparum 3D7 strain of some new 1-aryl-3-substituted propanol derivatives. Twelve of the tested compounds showed an IC50 lower than 1 µM. These compounds were also tested for cytotoxicity in murine J774 macrophages. The most active compounds were evaluated for in vivo activity against P. berghei in a 4-day suppressive test. Compound 12 inhibited more than 50% of parasite growth at a dose of 50 mg/kg/day. In addition, an FBIT test was performed to measure