Ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5α,8α-epidioxycholest-6-en-3β-ol isolated from the mollusk Dolabrifera dolabrifera shows significant activity against Leishmania donovani

Clark, Kathryn E., Capper, Angela, Della Togna, Gina, Paul, Valerie J., Romero, Luz I., Johns, Timothy, Cubilla-Rios, Luis, and Capson, Todd L. (2013) Ecology- and bioassay-guided drug discovery for treatments of tropical parasitic disease: 5α,8α-epidioxycholest-6-en-3β-ol isolated from the mollusk Dolabrifera dolabrifera shows significant activity against Leishmania donovani. Natural Product Communications, 8 (11). pp. 1537-1540.

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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, 5α,8α-epidioxycholest-6-en-3β-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 µM towards the amastigote form of Leishmania donovani compared with an IC50 of 281 µM 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.

Item ID: 31917
Item Type: Article (Research - C1)
ISSN: 1555-9475
Keywords: marine invertebrate, antileishmanial, endoperoxide, chemical ecology
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Funders: Natural Sciences and Engineering Research Council of Canada Canadian Graduate Scholarship, Levinson Fellowship from the Smithsonian Tropical Research Institute-McGill Neotropical Environmental Option, Fogarty International Center’s International Cooperative Biodiversity Groups
Projects and Grants: Fogarty International Center’s International Cooperative Biodiversity Groups program (ICBG TW006634)
Date Deposited: 24 Apr 2014 06:09
FoR Codes: 06 BIOLOGICAL SCIENCES > 0602 Ecology > 060205 Marine and Estuarine Ecology (incl Marine Ichthyology) @ 45%
11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111706 Epidemiology @ 25%
03 CHEMICAL SCIENCES > 0301 Analytical Chemistry > 030104 Immunological and Bioassay Methods @ 30%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920404 Disease Distribution and Transmission (incl. Surveillance and Response) @ 50%
96 ENVIRONMENT > 9605 Ecosystem Assessment and Management > 960507 Ecosystem Assessment and Management of Marine Environments @ 30%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 20%
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