Isoflavonoids and other compounds from Psorothamnus arborescens with antiprotozoal activities.
Bioactivity-guided fractionation of the root extract of Psorothamnus arborescens yielded the new isoflavone 5,7,3',4'-tetrahydroxy-2'-(3,3-dimethylallyl)isoflavone (1a) and the new 2-arylbenzofuran 2-(2'-hydroxy-4',5'-methylenedioxyphenyl)-6-methoxybenzofuran-3-carbaldehyde (2), together with seven known compounds, including three isoflavones, fremontin (3a), glycyrrhisoflavone (4a), and calycosin (5), two pterocarpans, maackiain (6) and 4-hydroxymaackiain (7), one triterpene, oleanolic acid (8), and one chalcone, isoliquiritigenin (9). In addition, the structure of the isoflavone fremontin was revised using spectroscopic and chemical methods and was assigned the new structure 3a. The isoflavone 1a and the chalcone 9 displayed leishmanicidal activity with IC50 values of 13.0 and 20.7 microM, respectively, against Leishmania donovani axenic amastigotes. Calycosin (5) exhibited selective toxicity against Trypanosoma brucei brucei (IC50 12.7 microM) compared to L. donovani amastigotes and Vero cells (IC50 100 and 159 microM, respectively). These results prompted us to test a small group of structurally related isoflavones for their antitrypanosomal activities. Genistein and 7,3',4'-trihydroxyisoflavone displayed promising activity (IC50 values 4.2 and 7.1 microM, respectively) and selectivity (IC50 versus Vero cells: 32.9 and 135 microM, respectively). These studies suggest that the isoflavone skeleton deserves further investigation as a template for novel antileishmanial and trypanocidal compounds.
Salem
Manar M
MM
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Werbovetz
Karl A
KA
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002140:California; D002522:Chlorocebus aethiops; D007887:Fabaceae / Q000737:chemistry*; D019833:Genistein / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects*; D015394:Molecular Structure; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014709:Vero Cells
D000981:Antiprotozoal Agents; D007529:Isoflavones; D019833:Genistein