Mukanganyama S., Bezabih M., Robert M., Ngadjui B.T., Kapche G.F.W., Ngandeu F., Abegaz B.
Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, P.O. Box MP167, Mt. Pleasant, Harare, Zimbabwe; Department of Chemistry, University of Botswana, P. Bag 00704, Gaborone, Botswana; Department of Chemistry, University of Yaounde, Yaounde, Cameroon; Department of Chemistry, University of Dschang, Dschang, Cameroon
Mukanganyama, S., Biomolecular Interactions Analyses Group, Department of Biochemistry, University of Zimbabwe, P.O. Box MP167, Mt. Pleasant, Harare, Zimbabwe; Bezabih, M., Department of Chemistry, University of Botswana, P. Bag 00704, Gaborone, Botswana; Robert, M., Department of Chemistry, University of Yaounde, Yaounde, Cameroon; Ngadjui, B.T., Department of Chemistry, University of Yaounde, Yaounde, Cameroon; Kapche, G.F.W., Department of Chemistry, University of Yaounde, Yaounde, Cameroon; Ngandeu, F., Department of Chemistry, University of Dschang, Dschang, Cameroon; Abegaz, B., Department of Chemistry, University of Botswana, P. Bag 00704, Gaborone, Botswana
Glutathione transferase P1-1 is over expressed in some cancer cells and contributes to detoxification of anticancer drugs, leading to drug-resistant tumors. The inhibition of human recombinant GSTP1-1 by natural plant products was investigated using 10 compounds isolated from plants indigenous to Southern and Central Africa. Monochlorobimane and 1-chloro-2,4-dinitrobenzene were used to determine GST activity. Each test compound was screened at 33 and 100 μM. Isofuranonapthoquinone (1) (from Bulbine frutescens) showed 68% inhibition at 33 μM, and sesquiterpene lactone (2) (from Dicoma anomala) showed 75% inhibition at 33 μM. The IC 50 value of 1 was 6.8 μM. The mode of inhibition was mixed, partial (G site) and noncompetitive (H site) with Ki values of 8.8 and 0.21 μM, respectively. Sesquiterpene 2 did not inhibit the CDNB reaction. Therefore, isofuranonapthoquinone 1 needs further investigations in vivo because of its potent inhibition of GSTP1-1 in vitro. © 2011 Informa UK, Ltd.
enzyme inhibitor; glutathione transferase P1; glutathione transferase p1 1; isofuranonaphthoquinone; natural product; plant extract; sesquiterpene lactone; unclassified drug; article; drug effect; drug potency; drug screening; enzyme activity; enzyme inhibition; human; IC 50; priority journal; Biological Agents; Cell Proliferation; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors; Glutathione S-Transferase pi; Humans; Isoenzymes; Kinetics; Molecular Conformation; Plant Extracts; Recombinant Proteins; Stereoisomerism; Structure-Activity Relationship; Bulbine frutescens; Dicoma anomala