2-substituted-3,11-bis Oxo Synthesis And Anti-tumor Activity -18β- Oleanane -29- 12-ene-lactam Compounds

Malignant neoplasm, called cancer, is a general and frequently-occurring disease which threatens human health seriously. It leads the second morality rate, inferior to cardiovascular disease. Many scientists over the world are very interested in that the natural products as lead compounds are modified to discover novel anti-tumor agents.18β-glycyrrhetinic acid and oleanolic acid as pentacyclic triterpenoids, are ubiquitous in the plant kingdom and exhibit various biological activities. Their structures are very similar and they are all potential anti-tumor promoters and cytotoxic agents against tumor cells, inhibiting proliferation, inducing apoptosis and preventing invasion. 18β-glycyrrhetinic acid was taken as the leading compound and ring A and 29-carboxyl group were modified. 2-hydroxymethylene-3,11-dioxo-18β-olean-12-ene-29-oic acid amides, 11-oxo-2,12-dieno-[2,3-d]isoxazol-18β-olean-29-oic acid amides, 2-cyano-3,11-dioxo-18β-olean-12-ene-29-oic-acid amides, 2-cyano-3,11-dioxo-18β-olean-1,12-diene-29-oic acid amides, twenty 18β-glycyrrhetinic acid derivatives were designed and synthesized, and their structures have been characterized by the application of ¹H-NMR, ¹³C-NMR and LC-MS.The growth inhibition and apoptosis induction ability of the target compounds were tested in HL-60 by the trypan blue dye exclusion and staining with acridine orange（AO） and ethidium bromide（EB）by fluorescence microscopy respectively. All of the target compounds showed potent anticaneer activity comparing with 18β-glycyrrhetinic acid, and G4, G6, G10, G20, G21, G22, G23 are worthy to investigate further, which have significant growth inhibition and inducing apoptosis.