INHIBITORY EFFECT OF URSOLIC ACID DERIVATIVES ON RECOMBINANT HUMAN ALDOSE REDUCTASE

2011 Eun Ha Lee*, S. A. Popov**, Joo Young Lee*, A. V. Shpatov**, T. P. Kukina**, Suk Woo Kang*, Cheol-Ho Pan*, Byung Hun Um*, Sang Hoon Jung*

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*Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340, Gangwon-do, Republic of Korea;
**Novosibirsk Institute of Organic Chemistry, Novosibirsk, Russian Federation

Received January 14, 2011; in final form, March 14, 2011

Aldose reductase (AR) is the first enzyme in the polyol pathway. AR has been reported to play an important role in the pathogenesis of diabetic complications. Ursolic acid and fourteen synthetic derivatives with ursane skeleton were tested for recombinant human aldose reductase (rhAR) inhibitory activity for development of diabetic complications. Among them, N-(3β-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) showed most potent rhAR inhibitory activity in vitro. Inhibition mode of N-(3β-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) was tested uncompetitively by kinetic analysis using the Lineweaver-Burk plots. Ursolic acid derivative N-(3β-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid is able to inhibit rhAR uncompetitively and could be offered as a lead compound for AR inhibition.

Keywords: aldose reductase; N-(3β-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid; ursolic acid derivatives; diabetic complications.

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These authors contributed equally to this work.

. 2011, 37 (5): 637-644