title: Heptyl prodigiosin, a bacterial metabolite, is antimalarial in vivo and non-mutagenic in vitro.
abstract: Heptyl prodigiosin was purified from a culture of alpha-proteobacteria isolated from a marine tunicate collected in Zamboanga, Philippines, as part of a program to screen natural products for antiparasitic activity. An in vitro antimalarial activity similar to that of quinine was found against the chloroquine-sensitive strain Plasmodium falciparum 3D7. The in vitro antimalarial activity was about 20 times the in vitro cytotoxic activity against L5178Y mouse lymphocytes. A single subcutaneous administration of 5 and 20 mg/kg significantly extended survival of P. berghei ANKA strain-infected mice but also caused sclerotic lesions at the site of injection. A single administration by gavage of 50 mg/kg did not increase survival time. The compound was not found to be mutagenic using in vitro micromethods for the Ames Salmonella typhimurium assay and the micronucleus assay using L5178Y mouse lymphoma cells.
authors.affiliation: INSERM U511, Immuno-Biologie Cellulaire et Moléculaire des Infections Parasitaires, Centre Hospitalo-Universitaire Universitaire Pitié-Salpêtriére, Université Pierre et Marie Curie, 75013 Paris, France. jaylazaro@hotmail.com
authors.forename: J Enrico H
authors.initials: JE
authors.lastname: Lazaro
authors.forename: Josiane
authors.initials: J
authors.lastname: Nitcheu
authors.forename: Rey Z
authors.initials: RZ
authors.lastname: Predicala
authors.forename: Gina C
authors.initials: GC
authors.lastname: Mangalindan
authors.forename: Fabrice
authors.initials: F
authors.lastname: Nesslany
authors.forename: Daniel
authors.initials: D
authors.lastname: Marzin
authors.forename: Gisela P
authors.initials: GP
authors.lastname: Concepcion
authors.forename: Bertrand
authors.initials: B
authors.lastname: Diquet
mesh_terms: D020561:Alphaproteobacteria / Q000378:metabolism*; D000818:Animals; D000962:Antimalarials / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects* / Q000302:isolation & purification; D010963:Plasmodium falciparum / Q000187:drug effects*; D011353:Prodigiosin / Q000031:analogs & derivatives / Q000302:isolation & purification* / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: D000962:Antimalarials; C473964:heptylprodigiosin; D011353:Prodigiosin