Department of Biochemistry, University of Zimbabwe, P.O. Box MP167, Mt. Pleasant, Harare, Zimbabwe.
J Enzyme Inhib Med Chem. 2011 Aug;26(4):460-7. doi: 10.3109/14756366.2010.526769. Epub 2010 Oct 28.
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 K(i) 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.
谷胱甘肽转移酶 P1-1 在一些癌细胞中过表达，并有助于解毒抗癌药物，导致肿瘤耐药。使用从南非和中非土生土长的植物中分离出的 10 种化合物，研究了天然植物产物对人重组 GSTP1-1 的抑制作用。单氯代丁烷和 1-氯-2,4-二硝基苯用于测定 GST 活性。每种测试化合物在 33 和 100μM 下进行筛选。异呋喃并萘醌（1）（来自 Bulbine frutescens）在 33μM 时显示出 68%的抑制率，倍半萜内酯（2）（来自 Dicoma anomala）在 33μM 时显示出 75%的抑制率。1 的 IC50 值为 6.8μM。抑制模式为混合、部分（G 位）和非竞争性（H 位），K(i) 值分别为 8.8 和 0.21μM。倍半萜 2 不能抑制 CDNB 反应。因此，由于其对 GSTP1-1 的体外抑制作用很强，异呋喃并萘醌 1 需要进一步的体内研究。
