title: Glutathione S-transferase inhibiting chemical constituents of Caesalpinia bonduc.
abstract: Glutathione S-transferase inhibition assay-guided fractionations on the ethanolic extract of the bark of Caesalpinia bonduc resulted in the isolation of a new sterol, 17-hydroxy-campesta-4,6-dien-3-one (1) along with four known compounds, 13,14-seco-stigmasta-5,14-dien-3alpha-ol (2), 13,14-seco-stigmasta-9(11),14-dien-3alpha-ol (3), caesaldekarin J (4) and pipataline (5) as active constituents. Structures of compounds 1-5 were established on the basis of extensive NMR spectroscopic studies. The compounds (1-5) were isolated on the basis of their inhibitory activity against glutathione S-transferase, an enzyme that has been implicated in resistances during treatment of cancer and parasitic infections. Efforts to study structure-activity relationships of compounds 2 and 3 were also made by modifying their structures. The IC50 values of these compounds and their derivatives ranged from 57-380 microM and were compared to the inhibitory effects due to sodium taurocholate, an isoprene-derived GST inhibitor (IC50=398 microM). A plausible biosynthesis of 13,14-seco-steroids has also been proposed.
authors.affiliation: Department of Chemistry, The University of Winnipeg, Winnipeg, Manitoba, Canada.
authors.forename: Chibuike C
authors.initials: CC
authors.lastname: Udenigwe
authors.forename: Athar
authors.initials: A
authors.lastname: Ata
authors.forename: Radhika
authors.initials: R
authors.lastname: Samarasekera
mesh_terms: D029911:Caesalpinia / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010840:Phytosterols / Q000737:chemistry* / Q000494:pharmacology*; D024301:Plant Bark / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D010840:Phytosterols; D005982:Glutathione Transferase