Current Organic Chemistry

Author(s): Nalin Seixas, Ionara I. Dalcol*, Bruno Ravanello, Keiti Alessio, Fábio A. Duarte, Vanessa Bender and Ademir F. Morel

DOI: 10.2174/1385272823666191014154939

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Evaluation of Acetylcholinesterase and Prolyl Oligopeptidase Inhibition of Novel Amino acid-functionalized Stigmasterol and Ursolic Acid Derivatives

Page: [2131 - 2140] Pages: 10

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Abstract

Triterpenes and phytosterols are classes of natural compounds widespread in plants possessing a great number of pharmacological activities. In our continued search for new compounds from natural sources with pharmacological potential, we prepared a series of novel stigmasterol and ursolic acid (UA) derivatives by coupling with L-proline, L-cysteine and L-glutamic acid. Unlike stigmasterol, the eight derivatives obtained showed good inhibitory capacity against acetylcholinesterase (AChE) or prolyl oligopeptidase (POP). Among these derivatives, we highlight 3 and 5 with IC50 values of 99.0 ± 8.8 and 97.5 ± 5.0 µM against AChE, respectively, and derivative 8 with a POP IC50 value of 75.7 ± 6.3 µM. The ursolic acid derivative 19 was the most promising compound of its class, with IC50 against AChE of 98.3 ± 7.7 µM. These results demonstrate that simple structural modifications on triterpenes and phytosterols can enhance their performance as enzymatic inhibitors.

Keywords: Sterols, triterpenes, stigmasterol derivatives, ursolic acid derivatives, acetylcholinesterase, prolyl oligopeptidase.