title: Northalrugosidine is a bisbenzyltetrahydroisoquinoline alkaloid from Thalictrum alpinum with in vivo antileishmanial activity.
abstract: Screening of a plant-derived natural product library led to the observation of in vitro antileishmanial activity by three bisbenzyltetrahydroisoquinoline alkaloids (1-3) that were purified previously from Thalictrum alpinum. A spectroscopic study of the active compounds was conducted to confirm their identities. Of the compounds tested, northalrugosidine (1) showed the most potent in vitro activity against Leishmania donovani promastigotes (0.28 μM) and the highest selectivity (29.3-fold) versus its general cytotoxicity against HT-29 human colon adenocarcinoma cells. Northalrugosidine was tested in vivo using a murine model of visceral leishmaniasis, resulting in the observation of a dose-dependent reduction of the parasitic burden in the liver and spleen without overt toxicity effects at 2.8, 5.6, and 11.1 mg/kg per animal when administered intravenously. This represents the first report of a bisbenzyltetrahydroisoquinoline alkaloid with in vivo efficacy against visceral leishmaniasis.
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors: C Benjamin
authors: CB
authors: Naman
authors: ‡Department of Pathology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Gaurav
authors: G
authors: Gupta
authors: ‡Department of Pathology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Sanjay
authors: S
authors: Varikuti
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Heebyung
authors: H
authors: Chai
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Raymond W
authors: RW
authors: Doskotch
authors: ‡Department of Pathology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
authors: Abhay R
authors: AR
authors: Satoskar
authors: †Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
authors: A Douglas
authors: AD
authors: Kinghorn
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000473:pathology; D008099:Liver / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry; D013154:Spleen / Q000187:drug effects; D031949:Thalictrum / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D007546:Isoquinolines; C000598716:northalrugosidine
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