title: Ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5alpha,8alpha-epidioxycholest-6-en-3beta-ol isolated from the mollusk Dolabrifera dolabrifera shows significant activity against Leishmania donovani.
abstract: An ecology- and bioassay-guided search employed to discover compounds with activity against tropical parasitic diseases and cancer from the opisthobranch mollusk, Dolabrifera dolabrifera, led to the discovery of antileishmanial properties in the known compound, 5alpha,8alpha-epidioxycholest-6-en-3beta-ol (1). Compound 1 was identified through nuclear magnetic resonance spectroscopy (1H, 13C) and mass spectrometry. The compound was concentrated in the digestive gland of D. dolabrifera, but was not detected in other body parts, fecal matter or mucus. Compound 1 showed an IC50 of 4.9 microM towards the amastigote form of Leishmania donovani compared with an IC50 of 281 microM towards the control Vero cell line, a 57.3-fold difference, and demonstrated no measurable activity against Plasmodium falciparum, Trypanosoma cruzi, and the breast cancer cell line, MCF-7.
authors.affiliation: Smithsonian Tropical Research Institute, Apartado 2072, Balboa Ancón, Republic of Panama.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Clark
authors.affiliation: Smithsonian Marine Station at Fort Pierce, 701 Seaway Drive, Fort Pierce, Florida 34949, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Capper
authors.affiliation: Instituto de Investigaciones Científicas Avanzadas y Servicios de Alta Tecnología, Clayton, Edificio 175, PO Box 7250, Panama City, Republic of Panama.
authors.forename: Gina
authors.initials: G
authors.lastname: Della Togna
authors.affiliation: Smithsonian Marine Station at Fort Pierce, 701 Seaway Drive, Fort Pierce, Florida 34949, USA.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Paul
authors.affiliation: Instituto de Investigaciones Científicas Avanzadas y Servicios de Alta Tecnología, Clayton, Edificio 175, PO Box 7250, Panama City, Republic of Panama.
authors.forename: Luz I
authors.initials: LI
authors.lastname: Romero
authors.affiliation: Department of Plant Science, McGill University, 21,111 Lakeshore, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Johns
authors.affiliation: Laboratorio de Bioorgánica Tropical, Departamento de Química Orgánica, Universidad de Panamá, Apartado 0824-10835, Panama City, Republic of Panama.
authors.forename: Luis
authors.initials: L
authors.lastname: Cubilla-Rios
authors.affiliation: Smithsonian Tropical Research Institute, Apartado 2072, Balboa Ancón, Republic of Panama.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Capson
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000302:isolation & purification* / Q000494:pharmacology; D001681:Biological Assay; D055808:Drug Discovery; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects*; D008974:Mollusca / Q000737:chemistry*
chemical_list: C503471:5alpha,8alpha-epidioxyergosta-6,22-dien-3-beta-ol; D000981:Antiprotozoal Agents; D004875:Ergosterol