title: Antiprotozoal isoflavan quinones from Abrus precatorius ssp. africanus.
abstract: A library of 206 extracts from selected South African plants was screened in vitro against a panel of protozoan parasites, Plasmodium falciparum, Trypanosoma brucei rhodesiense, and Leishmania donovani. A CH2Cl2/MeOH (1 : 1) extract of Abrus precatorius L. ssp. africanus strongly inhibited P. falciparum (98 %), T. b. rhodesiense (100 %), and L. donovani (76 %) when tested at a concentration of 10.0 µg/mL. The active constituents were tracked by HPLC-based activity profiling and isolated by preparative and semipreparative RP-HPLC chromatography. Structures were established by HR-ESIMS, and 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC, and NOE difference spectroscopy). Five compounds were obtained and identified as two isoflavan hydroquinones, abruquinone H (1) and abruquinone G (2), and three isoflavan quinones, abruquinone I (3), abruquinone B (4), and 7,8,3''5'-tetramethoxyisoflavan-1',4'-quinone (5). Compounds 1 and 3 were new natural products. The absolute configuration of compounds was determined by comparison of electronic circular dichroism spectra with calculated ECD data. Compounds 3 and 4 showed strong activity against T. b. rhodesiense (IC50 values of 0.30 and 0.16 µM, respectively) and good selectivity (selectivity indices of 73.7 and 50.5, respectively).
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Hata
authors.forename: Melanie
authors.initials: M
authors.lastname: Raith
authors.forename: Samad Nejad
authors.initials: SN
authors.lastname: Ebrahimi
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zimmermann
authors.forename: Tsholofelo
authors.initials: T
authors.lastname: Mokoka
authors.forename: Dashnie
authors.initials: D
authors.lastname: Naidoo
authors.forename: Gerda
authors.initials: G
authors.lastname: Fouche
authors.forename: Vinesh
authors.initials: V
authors.lastname: Maharaj
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D029912:Abrus / Q000737:chemistry*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000187:drug effects*; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D011809:Quinones