Design, Synthesis and Biological Evaluation of Potent Human Glyoxalase I Inhibitors.
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 Kivalue 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 (Ki=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.
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Tian
T
Jin
School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yet-Sen University.
Jing
J
Zhai
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Xiao
X
Liu
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Yan
Y
Yue
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Maolin
M
Huang
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Zonghe
Z
Li
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Caixia
C
Ni
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Qishan
Q
Deng
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Yankui
Y
Sang
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Zhongwei
Z
Yao
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Hong
H
Zhang
School of Pharmaceutical Sciences & Centre for Cellular and Structural Biology of Sun Yet-Sen University.
Xiaopeng
X
Hu
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Insititute of Antibiotics, Chengdu University.
Zhe-Bin
ZB
Zheng
D000818:Animals; D001681:Biological Assay; D045744:Cell Line, Tumor; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D047368:Tumor Burden / Q000187:drug effects
D004791:Enzyme Inhibitors; D004952:Esters; D007791:Lactoylglutathione Lyase; D005978:Glutathione
NCI-H522 cell line; cell membrane permeability study; glyoxalase I inhibitor; inhibition constant; synthesis