Synthesis of nitrogen-containing oleanolic acid derivatives as carbonic anhydrase and acetylcholinesterase inhibitors

Abstract

In this study, a total of 13 compounds (5-17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds (10, 11, 12, 15 and 17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. Compounds 13 and 15 showed better inhibitory activity than the other compounds against both hCA I and hCA II isoenzymes, which are competing with AZA. In addition, compound 15 showed the strongest AChE inhibitory activity among all the tested compounds, with an IC50 value of 34.46 mu M.