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.
Li
Jun-Feng
JF
Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Zhao
Yu
Y
Cai
Min-Min
MM
Li
Xiao-Fei
XF
Li
Jian-Xin
JX
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008297:Male; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D006571:Heterocyclic Compounds; D009828:Oleanolic Acid