Preparation, anticholinesterase activity and molecular docking of new lupane derivatives

MARIA JULIA CASTRO; RICHMOND, VICTORIA; CARMEN ROMERO; MAIER, MARTA SILVIA; ANA ESTÉVEZ-BRAUN; RAVELO, ANGEL G.; FARAONI, MARÍA BELEN; ANA PAULA MURRAY

BIOORGANIC & MEDICINAL CHEMISTRY.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014 vol. 22 p. 3341 - 3350

0968-0896

A set of twenty one lupane derivatives (2-22) was prepared from the natural triterpenoid calenduladiol (1) by transformations on the hydroxyl groups at C-3 and C-16, and also on the isopropenyl moiety. The derivatives were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and some structure-activity relationships were outlined with the aid of enzyme kinetic studies and docking modelization. The most active compound resulted to be 3,16,30-trioxolup-20(29)-ene (22), with an IC50 value of 21.5 µM for butyrylcholinesterase, which revealed a selective inhibitor profile towards this enzyme.