Synthesis of Oleanolic Acid Dimers as Inhibitors of Glycogen Phosphorylase |
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| Authors: | Keguang Cheng Jun Liu Hongbin Sun Juan Xie |
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| Institution: | 1. PPSM, ENS Cachan, CNRS, UniverSud, 61 av President Wilson, F‐94230 Cachan, (phone: +33?1?47405586;2. fax: +33?1?47402454);3. Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24?Tongjiaxiang, Nanjing 210009, P.?R. China (phone: +86?25?85327950;4. fax: +86?25?83271335);5. Jiangsu Center for Drug Screening, China Pharmaceutical University, 1 Shennonglu, Nanjing 210038, P.?R. China |
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| Abstract: | Recently, oleanolic acid was found to be an inhibitor of glycogen phosphorylase. For further structural modification, we have synthesized several dimers of oleanolic acid by using amide, ester, or triazole linkage with click chemistry. The click chemistry was shown to be the most efficient method for the dimer synthesis. Nearly quantitative yield of triazole‐linked dimers was obtained. Biological evaluation of the synthesized dimers as inhibitors of glycogen phosphorylase has been described. Four of six dimers exhibited inhibitory activity against rabbit muscle glycogen phosphorylase a (RMGPa), with compounds 2 and 7 as the most potent inhibitors, which displayed an IC50 value (ca. 3 μM ) lower than that of oleanolic acid (IC50=14 μM ). |
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| Keywords: | Inhibitors Glycogen phosphorylase inhibitors Oleanolic acid Click chemistry |
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