Cynaropicrin: the first plant natural product with in vivo activity against Trypanosoma brucei

Planta medica
Stefanie ZimmermannMichael Adams

Abstract

A screen of 1800 plant and fungal extracts with subsequent HPLC-based activity profiling was done to identify new antiprotozoal leads from nature. This led to the identification of cynaropicrin (1) from the herb CENTAUREA SALMANTICA L. (Asteraceae) as a potent IN VITRO inhibitor of TRYPANOSOMA BRUCEI RHODESIENSE. It preferentially inhibited T. B. RHODESIENSE (IC (50) of 0.3 µM) and T. BRUCEI GAMBIENSE (IC (50) of 0.2 µM), compared to TRYPANOSOMA CRUZI (IC (50) of 4.4 µM) and PLASMODIUM FALCIPARUM (IC (50) of 3.0 µM). Testing against melarsoprol- and pentamidine-resistant strains (IC (50)s of 0.3 µM and 0.1 µM, respectively) showed no cross-resistance. Intraperitoneal administration of 2 × 10 mg/kg body weight/day in the T. B. RHODESIENSE STIB 900 acute mouse model led to a 92 % reduction of parasitemia compared to untreated controls on day seven post-infection. Removal of the 2-hydroxymethyl-2-propenoyl moiety of cynaropicrin led to a loss of toxicity towards T. B. RHODESIENSE. Cytotoxicities against rat myoblasts (L6 cells), human colon adenocarcinoma cells, and murine peritoneal macrophages were measured, and selectivity indices of 7.8, 62, and 9.5 were determined. This is the first report of a plant natural product with pote...Continue Reading

Citations

Jun 22, 2012·PLoS Neglected Tropical Diseases·Vincent JamonneauBruno Bucheton
Mar 8, 2012·Scientia pharmaceutica·Stefanie ZimmermannMichael Adams
Mar 26, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Stefanie ZimmermannMichael Adams
Oct 23, 2013·Future Medicinal Chemistry·Lori FerrinsJonathan B Baell
Jun 20, 2012·Journal of Ethnopharmacology·Michael AdamsMatthias Hamburger
Jan 3, 2014·Fitoterapia·Yoshie HataMatthias Hamburger
Jan 6, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chonny Herrera AcevedoMarcus Tullius Scotti
Jan 25, 2017·Journal of Natural Products·Maria De MieriMatthias Hamburger
Jan 18, 2014·Bioorganic & Medicinal Chemistry Letters·Toyonobu UsukiMichael Adams
Aug 14, 2013·Antimicrobial Agents and Chemotherapy·Cristiane França da SilvaMaria de Nazaré Correia Soeiro
Jul 26, 2013·Natural Product Reports·Braulio M Fraga
Dec 23, 2016·Frontiers in Pharmacology·Mahmoud F ElsebaiAtanas G Atanasov
Jan 16, 2021·Scientific Reports·Sara SorouryMahdi Moridi Farimani
May 14, 2021·Organic & Biomolecular Chemistry·Tenma NakamuraToyonobu Usuki
Sep 9, 2021·Clinical Microbiology Reviews·Oyelola AdegboyeClaire Loiseau

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