title: Antitrypanosomal isoflavan quinones from Abrus precatorius.
abstract: Human African trypanosomiasis is a neglected tropical disease in sub Saharan Africa that is fatal if left untreated. In a search for new natural products with antitrypanosomal activity, we recently identified abruquinones B and I from Abrus precatorius as potent in vitro trypanocidal compounds with high selectivity indices. To obtain sufficient compound for in vivo efficacy tests in mice, a second batch of plant material was re-collected and extracted. However, the chemical profiles of the two batches differed, and additional abruquinones were isolated and identified by HR-ESI-MS, and 1D and 2D NMR ((1)H, (13)C, COSY, HMBC, HSQC, and NOESY) spectroscopy. Abruquinones J (1), K (2), and L (3) were new, while abruquinones A (4) and D (5) were known from the first batch of plant material. The absolute configuration of compounds 1 to 3 was determined by comparison of electronic circular dichroism (ECD) spectra with calculated ECD data. Compounds 2 to 5 showed high in vitro activity against T. b. rhodesiense (IC50 of 0.01, 0.02, 0.02 and 0.01 μM, respectively), and remarkable SIs of 508, 374, 1379, and 668, respectively.
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland; Department of Pharmacy, Faculty of Sciences, National University of Colombia, Carrera 30 No. 45-03, Bogota D.C. 111321, Colombia.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Hata
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland; Department of Phytochemistry, Medicinal Plant and Drugs Research Institute, Shahid Beheshti University, G. C., Tehran, Iran.
authors.forename: Samad Nejad
authors.initials: SN
authors.lastname: Ebrahimi
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: De Mieri
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: Biosciences, Council for Scientific and Industrial Research (CSIR), PO Box 395, Pretoria 0001, South Africa.
authors.forename: Tsholofelo
authors.initials: T
authors.lastname: Mokoka
authors.affiliation: Biosciences, Council for Scientific and Industrial Research (CSIR), PO Box 395, Pretoria 0001, South Africa.
authors.forename: Dashnie
authors.initials: D
authors.lastname: Naidoo
authors.affiliation: Biosciences, Council for Scientific and Industrial Research (CSIR), PO Box 395, Pretoria 0001, South Africa.
authors.forename: Gerda
authors.initials: G
authors.lastname: Fouche
authors.affiliation: Biosciences, Council for Scientific and Industrial Research (CSIR), PO Box 395, Pretoria 0001, South Africa.
authors.forename: Vinesh
authors.initials: V
authors.lastname: Maharaj
authors.affiliation: Swiss Tropical and Public Health Institute and University of Basel, Socinstrasse 57, CH-4002 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Swiss Tropical and Public Health Institute and University of Basel, Socinstrasse 57, CH-4002 Basel, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Potterat
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Electronic address: matthias.hamburger@unibas.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D029912:Abrus / Q000737:chemistry*; D000818:Animals; D001578:Benzopyrans / Q000302:isolation & purification / Q000633:toxicity; D016227:Benzoquinones / Q000302:isolation & purification / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D051381:Rats; D014344:Trypanocidal Agents / Q000302:isolation & purification*
chemical_list: D001578:Benzopyrans; D016227:Benzoquinones; D014344:Trypanocidal Agents; C093391:abruquinone A
keywords: Abrus precatorius; ECD; Fabaceae; Isoflavan quinone; Trypanosoma brucei rhodesiense