Planta Med 2012; 78 - PD39
DOI: 10.1055/s-0032-1320397

Synthesis and antimalarial activity of fagaronine

M Rivaud 1, A Mendoza 1, 2, M Sauvain 1, 3, A Valentin 1, V Jullian 1
  • 1UMR152 (Pharmacochimie et Pharmacologie pour le Développement-PHARMA DEV), IRD-Université de Toulouse, UPS, Toulouse, France
  • 2Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiologia Aplicada (CIFA), Universidad de Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain
  • 3UMR 152, IRD, Mission IRD Casilla 18–1209 Lima, Peru

Fagaronine 1, a benzo[c]phenanthridine first isolated from Fagara zanthoxyloïdes in 1972 is known for its in vitro activity against P. falciparum in the nanomolar range. In order to study its antimalarial potential further, we performed a short synthesis for this molecule, inspired from the synthesis already published by Luo for nornitidine. This allowed us to obtain fagaronine 1 in 7 steps with a 10% yield. The key step is a nickel catalyzed annulation reaction between alkyne 5 and bromobenzaldehyde 3.

An antimalarial activity in vivo on mice comparable to the activity of chloroquine was evidenced. Fagaronine appears as a good potential lead for the design of new antimalarial molecules.