New 1-aryl-3-substituted propanol derivatives as antimalarial agents.
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 IC(50) lower than 1 microM. 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 the ability to inhibit ferriprotoporphyrin biocrystallization. This data indicates that 1-aryl-3-substituted propanol derivatives hold promise as a new therapeutic option for the treatment of malaria.
Pérez-Silanes
Silvia
S
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain. sperez@unav.es
Berrade
Luis
L
García-Sánchez
Rory N
RN
Mendoza
Adela
A
Galiano
Silvia
S
Pérez-Solórzano
Berta Martín
BM
Nogal-Ruiz
Juan J
JJ
Martínez-Fernández
Antonio R
AR
Aldana
Ignacio
I
Monge
Antonio
A
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D020005:Propanols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000962:Antimalarials; D020005:Propanols