Synthesis and Anti-Tumor Activities of Ring A Derived Analogues of Oleanolic Acid

By means of computer aided drug design, simulation of apoptosis inhibiting protein complex glycine receptor kinase C-kit docking with active small molecules. Ten analogues were successfully synthesized by the introduction of nitrogen-containing heterocyclic compounds at ring A and the modification of the esterification and amidation at C(28) position in the natural product oleanolic acid. Their structures were charachterized by H-1 NMR, C-13 NMR, MS and so forth. Their anti-tumor activities against KB, A549 cells in vitro were evaluated by methyl thiazolyl tetrazolium (MTT) assay. These results indicated that the objective of test compounds of two kinds of tumor cells have good inbitory activity, and 5',6'-dihydro-olean2-ene-[2,3-b]pyrazin-12-ene-28-acy1-4 ''-monomethylaniline (I-4) (IC50 = 2.67 mon) and olean-2-ene-[2,3-b]pyrimidine-12-ene-28-oic acid n-hextyl ester (II3) (IC50=1.03 mu mol/L have especially more potent inbitory activity on A549 tumor cells than 5-fluorouracil (IC50=7.39 mol/L, which are worthy to be studied further.