Obtenção de derivados semissintéticos do alcaloide (-)-cassina na busca por compostos com potencial antimalárico

Abstract

The present work was motivated by preliminary studies that verified the antimalarial activity of the alkaloids (–)-cassine and (–)-spectaline, that were isolated of flowers from Senna spectabilis. Whereas that there are few drugs for the treatment of malaria, one of the neglected diseases that plagues most developing countries, a series of semisynthetic derivatives from (–)-cassine was planned, aiming at obtaining more powerful compounds that can be used as models for the development of new antimalarial drugs. Initially, the serie of planned esters was subjected to a virtual screening using the molecular docking tool to evaluate the affinity between analogues and the enzyme lactate desydrogenase, the main target of antimalarial drugs. Then the most promising derivatives were synthesized and obtained with good yields: (‒)-3-O-acetylcassine (48%), 3-O-butanoylcassine (67%), 3-O-pentanoylcassine (52%), 3-O-hexanoylcassine (58%), 3-O-heptanoylcassine (65%), 3-O-(2-bromobenzoyl)-cassine (76%), 3-O-(3-bromobenzoyl)cassine (74%), 3-O-(4-bromobenzoyl)cassine (79%), 3-O-(2-clorobenzoyl)-cassine (64%), 3-O-(3-clorobenzoyl)cassine (71%), 3-O-(4-clorobenzoyl)cassine (76%), 3-O-(2-metilbenzoyl)-cassine (56%), 3-O-(3-metilbenzoyl)cassine (63%), 3-O-(4-metilbenzoyl)cassine (59%), 3-O-(2-nitrobenzoyl)-cassine (67%), 3-O-(3-nitrobenzoyl)cassine (62%), 3-O-(4-nitrobenzoyl)cassine (74%). These compounds were characterized by spectroscopic (nuclear magnetic ressonance) and spectrometric (mass spectrometry) techniques.