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

• Published in: Medicinal chemistry research Vol. 32; no. 4; pp. 694 - 704
• Main Authors: Şenol, Halil, Çelik Turgut, Gurbet, Şen, Alaattin, Sağlamtaş, Rüya, Tuncay, Salih, Gülçin, İlhami, Topçu, Gülaçtı
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2023; Springer Nature B.V
• Subjects: Acetylcholinesterase; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Carbonic anhydrase; Carbonic anhydrase I; Carbonic anhydrase II; Chemical synthesis; Hydrazones; Inorganic Chemistry; Isoenzymes; Medicinal Chemistry; NMR; Nuclear magnetic resonance; Oleanolic acid; Original Research; Pharmacology/Toxicology; Oxime; Imine; Hydrazone; Carbonic anhydrase; Acetylcholinesterase; Oleanolic acid
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-023-03031-z

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 IC
50
value of 34.46 µM.