Jin Tian, Zhai Jing, Liu Xiao, Yue Yan, Huang Maolin, Li Zonghe, Ni Caixia, Deng Qishan, Sang Yankui, Yao Zhongwei, Zhang Hong, Hu Xiaopeng, Zheng Zhe-Bin
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yet-Sen University.
Chem Pharm Bull (Tokyo). 2017 May 1;65(5):455-460. doi: 10.1248/cpb.c16-00800. Epub 2017 Mar 17.
Several glutathione derivatives bearing the S-(N-aryl-N-hydroxycarbamoyl) or S-(C-aryl-N-hydroxycarbamoyl) moieties (10, 10', 13-15) were synthesized, characterized, and their human glyoxalase I (hGLO1) inhibitory activity was evaluated. Compound 10 was proved to be the effective hGLO1 inhibitor with a K value of 1.0 nM and the inhibition effect of compound 10 on hGLO1 was nearly ten-fold higher than that of the strongest inhibitor 2 (K=10.0 nM) which has been reported in the field of glutathione-type hGLO1 inhibitors. Its diethyl ester prodrug 10' was able to penetrate cell membrane and had good inhibitory effect on the growth of NCI-H522 cell xenograft tumor model.
