| Cancer is still a challenge for scientists. The cancer incidence is increasing according to years. Chemotherapy is the major therapeutic method, but because of the poor selectivity of some antineoplastic drugs, some side effects will occur. Natural products are proud of low toxicity and high efficacy, so they are usually used as leading compounds to discover novel anti-tumor agents.18β-glycyrrhetinic acid as pentacyclic triterpenoids exhibits various biological activities, such as ant-inflammation, anti-ulcer, anti-virus and anti-tumor. The mechanism of 18β-glycyr-rhetinic acid against cancer is associated with inhibiting proliferation, inducing apoptosis and preventing invasion.18β-glycyrrhetinic acid was taken as the leading compound whose ring A,11-carbonyl group and 29-carboxylic acid were modified.2-hydroxymethylene-3-oxo-olean-12-ene-29-oic acid amides, [2,3-d] isoxazol-olean-12-ene-29-oic acid amides,2-cyano-3-oxo-olean-12-ene-29-oic-acid amides,2-cyano-3-oxo-olean-1,12-diene-29-oic acid amides, twenty 18β-glycyrrhetinic acid derivatives were designed and synthesized. Their structures have been characterized by the application of1H-NMR, LC-MS, IR and 13C-NMR.The growth inhibition effect of target compounds was tested in PC-3 by MTT method. All of the modified compounds showed potent anticancer activity comparing with 18β-glycyr-rhetinic acid. Compound GLY-16 exhibited significant growth inhibition effect with GI50=6.97μM, which is worthy to investigate further. |
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