BORIONI JOSÉ LUIS
Congresos y reuniones científicas
Título:
Derivative of Solanocapsine as Inhibitors of Acetylcholinesterase
Autor/es:
JOSÉ L. BORIONI; MANUELA E. GARCÍA; MARCELO PUIATTI; ADRIANA B. PIERINI; V. CABALLARO; ANA MURRAY; ALICIA PEÑÉÑORY
Reunión:
Congreso; 10th Congress of the World Association of Theoretical and Computational Chemists (WATOC); 2014
Resumen:
The investigation of natural products in medicinal chemistry is really essential today. In this context, inhibitors of acetylcholinesterase (AChE) are actively search for a treatment of Alzheimer disease (AD). The AChE enzyme has a catalytic site at the bottom of deep narrow catalytic gorge and a peripheral anionic site (PAS) at the entrance. Achieving strong AChE inhibitors (AChEI) that interact with the catalytic site
does not represent a significant improvement unless concomitant inhibition of the PAS, which is associated with a neurotoxic cascade characteristic of AD. Simultaneous interaction with both sites of AChE has been suggested to be important in designing powerful and selective AChEI. In order to achieve interaction throughout all the
active site, new AChEIs include two components separated by a spacer group with a suitable length. Because of this, we employed as a template a steroidal alkaloid, isolatedfrom Solanum pseudocapsicum L. with an IC50 of 3.22 μM , Solanocapsine. Based on the above strategy, a series of new derivatives of solanocapsine were synthesized and their inhibitory activities on AChE tested. Structure activity relationships through molecular
docking studies and molecular dynamicswere then discussed. Based on these results the binding modes of the compounds were obtained and new derivatives are proposed.
does not represent a significant improvement unless concomitant inhibition of the PAS, which is associated with a neurotoxic cascade characteristic of AD. Simultaneous interaction with both sites of AChE has been suggested to be important in designing powerful and selective AChEI. In order to achieve interaction throughout all the
active site, new AChEIs include two components separated by a spacer group with a suitable length. Because of this, we employed as a template a steroidal alkaloid, isolatedfrom Solanum pseudocapsicum L. with an IC50 of 3.22 μM , Solanocapsine. Based on the above strategy, a series of new derivatives of solanocapsine were synthesized and their inhibitory activities on AChE tested. Structure activity relationships through molecular
docking studies and molecular dynamicswere then discussed. Based on these results the binding modes of the compounds were obtained and new derivatives are proposed.
