Derivatives of Solanocapsine as inhibitors of acetylcholinesterase

JOSÉ L. BORIONI; MANUELA E. GARCÍA; VALERIA CAVALLARO; ANA PAULA MURRAY; ALICIA B. PEÑÉÑORY; MARCELO PUIATTI; ADRIANA B. PIERINI

Santiago de Chile

Congreso; 10th Congress of the World Association of Theoretical and Computational Chemists; 2014

World Association of Theoretical and Computational Chemists

Today, the investigation of natural products in medicinal chemistry is really essential. In this context, inhibitors of acetylcholinesterase (AChE) are actively search for a treatment of Alzheimer´s disease (AD). Simultaneous interaction at the bottom of the deep narrow catalytic gorge and the peripheral anionic site (PAS) of AChE has been suggested to be important in designing powerful and selective AChEI. Because they can inhibit other steps in the cascade of AD. In order to achieve interaction throughout all the active site, we employed, as a template, a steroidal alkaloid solanocapsine, isolated from Solanum pseudocapsicum L.. A series of new derivatives were obtained, groups 1-5, and their inhibitory activities tested on Torpedo californica AChE (TcAChE). Structure-activity relationships through molecular docking studies and molecular dynamics were then discussed. Based on these results new derivatives are proposed.