Estudo cristaloquímico de benzofenonas preniladas extraídas de sementes e frutos de Rheedia brasiliensis: estrutura cristalina e relação estrutura-atividade

Abstract

The present Master degree dissertation contains two parts: the first one, which was devoted to extract preparation from Rheedia brasiliensis seeds and fruits in order to isolate bioactive polyprenylated benzophenones and to identify their molecular and crystalline structures, leads two articles on structural elucidation of two natural products by X-ray crystallography and spectroscopic techniques: guttiferone A and garciniaphenone; the second one is a paper describing the inhibiting activity of the two compounds before mentioned and other two benzophenone-type derivatives, epiclusianone, which was also isolated from Rheedia brasiliensis, and 2,2’,4- trihydroxybenzophenone, which was synthesized by aromatic electrophilic substitution, against four proteases, papain, trypsin, cathepsin B and cathepsin G. Garciniaphenone has been discovered for the first time in Rheedia brasiliensis fruits and its complete characterization is given on a paper of the series. The crystallographic structure of a HIV-inhibitory benzophenone that was initially isolated from Symphonia globulifera, guttiferone A, is reported on another article of the series. On both papers, the structures of garciniaphenone and guttiferone A are analyzed matching their steric, electronic and geometrical features to that found in the literature for epiclusianone and its epimer, clusianone, which has allowed to state relationships between configuration and keto-enol tautomerism. The article concerning the inhibiting effect of benzophenones on proteases shows experimental data that were correlated with certain structural motifs determined by X-ray diffraction crystallography, establishing structure-activity relationships strongly supported by theoretical investigations using computational docking to predict the inhibitor-enzyme complex interaction pattern.