Synthesis and evaluation of a novel series of heterocyclic oleanolic acid derivatives with anti-osteoclast formation activity.

Oleanolic acid with anti-bone resorption effect was an active component discovered in a medicinal plant of Achyranthes bidentata. A series of heterocyclic derivatives of oleanolic acid including indole, pyrazine, quinoxaline, quinoline moieties and their natural amino acid amides were synthesized. Their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) and cytotoxicity of the selected derivatives were evaluated. Among the derivatives, compounds 2a and 8a displayed quite a potent activity even at 200 nM. The structure-activity relationships of the derivatives were also discussed.