INQUISUR   21779
INSTITUTO DE QUIMICA DEL SUR
Unidad Ejecutora - UE
artículos
Título:
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids
Autor/es:
CASTRO, MARÍA JULIA; MURRAY, ANA PAULA; RICHMOND, VICTORIA; FARAONI, MARÍA BELÉN
Revista:
BIOORGANIC CHEMISTRY
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2018 vol. 79 p. 301 - 309
ISSN:
0045-2068
Resumen:
A set of triterpenoids with different grades of oxidation in the lupane skeleton were prepared and evaluated as cholinesterase inhibitors. Allylic oxidation with selenium oxide and Jones?s oxidation were employed to obtain mono-, di- and tri-oxolupanes, starting from calenduladiol (1) and lupeol (3). All the derivatives showed a selective inhibition of butyrylcholinesterase over acetylcholinesterase (BChE vs. AChE). A kinetic study proved that compounds 2 and 9, the more potent inhibitors of the series, act as competitive inhibitors. Molecular modeling was used to understand their interaction with BChE, the role of carbonyl at C-16 and the selectivity towards this enzyme over AChE. These results indicate that oxidation at C-16 of the lupane skeleton is a key transformation in order to improve the cholinesterase inhibition of these compounds.