title: Antitrypanosomal isothiocyanate and thiocarbamate glycosides from Moringa peregrina.
abstract: O-Methyl (1), O-ethyl (2), and O-butyl (3) 4-[(α-L-rhamnosyloxy) benzyl] thiocarbamate (E), along with 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (4) have been isolated from the aerial parts of Moringa peregrina. The compounds were tested for in vitro activity against Trypanosoma brucei rhodesiense and cytotoxicity in rat skeletal myoblasts (L6 cells). The most potent compound was 4 with an IC50 of 0.10 µM against T.b. rhodesiense and a selectivity index of 73, while the thiocarbamate glycosides 1, 2, and 3 showed only moderate activity. Intraperitoneal administration of 50 mg/kg body weight/day of 4 in the T.b. rhodesiense STIB 900 acute mouse model revealed significant in vivo toxicity. Administration of 10 mg/kg body weight/day resulted in a 95% reduction of parasitemia on day 7 postinfection, but did not cure the animals. Because of its high in vitro activity and its ability to irreversibly inhibit trypanothione reductase, an attractive parasite-specific target enzyme, 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate (4), can be considered as a lead structure for the development and characterization of novel antitrypanosomal drugs.
authors: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
authors: Mahdi
authors: M
authors: Ayyari
authors: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
authors: Peyman
authors: P
authors: Salehi
authors: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
authors: Samad Nejad
authors: SN
authors: Ebrahimi
authors: Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors: Stefanie
authors: S
authors: Zimmermann
authors: Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors: Lena
authors: L
authors: Portmann
authors: Center of Biochemistry, Heidelberg University, Heidelberg, Germany.
authors: R Luise
authors: RL
authors: Krauth-Siegel
authors: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors: Marcel
authors: M
authors: Kaiser
authors: Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors: Reto
authors: R
authors: Brun
authors: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G. C., Evin, Tehran, Iran.
authors: Hassan
authors: H
authors: Rezadoost
authors: Department of Pharmacognosy and Phytochemistry, Institute of Medicinal Plants, ACECR, Karaj, Iran.
authors: Shamsali
authors: S
authors: Rezazadeh
authors: Department of Pharmaceutical Sciences, Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors: Matthias
authors: M
authors: Hamburger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D029587:Moringa / Q000737:chemistry*; D032448:Myoblasts, Skeletal / Q000187:drug effects; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D035261:Plant Components, Aerial / Q000737:chemistry; D051381:Rats; D012210:Rhamnose / Q000031:analogs & derivatives* / Q000737:chemistry; D013859:Thiocarbamates / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology
chemical_list: C000592588:4-((alpha-L-rhamnosyloxy)benzyl)thiocarbamate; D006027:Glycosides; D013859:Thiocarbamates; D014344:Trypanocidal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase; D012210:Rhamnose