Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies.

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Yuan M, Luo M, Song Y, Xu Q, Wang X, Cao Y, Bu X, Ren Y, Hu X

Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies.

Bioorg Med Chem. 2011 Feb 1;19(3):1189-96. doi: 10.1016/j.bmc.2010.12.039. Epub 2010 Dec 22.

PubMed ID

21237663 [ View in PubMed

]

Abstract

Several recent developments suggest that the human glyoxalase I (GLO I) is a potential target for anti-tumor drug development. In present study, a series of curcumin derivatives with high inhibitory activity against human GLO I were discovered. Inhibition constant (K(i)) values of compounds 8, 9, 10, 11 and 13 to GLO I are 4.600muM, 2.600muM, 3.200muM, 3.600muM and 3.600muM, respectively. To elucidate the structural features of potent inhibitors, docking-based three-dimensional structure-activity relationship (3D-QSAR) analyses were performed. Satisfactory agreement between experiment and theory suggests that comparative molecular similarity index analysis (CoMSIA) modeling exhibit much better correlation and predictive power. The cross-validated q(2) value is 0.638 while no-validation r(2) value is 0.930. Integrated with docking-based 3D-QSAR CoMSIA modeling, molecular surface property (electrostatic and steric) mapping and molecular dynamics simulation, a set of receptor-ligand binding models and bio-affinity predictive models for rational design of more potent inhibitors of GLO I are established.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Indomethacin	Lactoylglutathione lyase	Ki (nM)	24000	N/A	N/A	Details
Indomethacin	Lactoylglutathione lyase	Ki (nM)	18100	N/A	N/A	Details