PHYTOCHEMICAL STUDY AND EVALUATION OF THE ANTI- Schistosoma mansoni POTENTIAL in vitro AND in vivo OF SPECIALIZED METABOLITES ISOLATED FROM Drimys brasiliensis (WINTERACEAE)
The present work aims to carry out phytochemical prospecting of the hexane extract from the twigs of the plant species Drimys brasiliensis (Winteraceae) in order to obtain special metabolites with anti-S. mansoni. When analyzing the hexane extract from the branches of D. brasiliensis, the presence of terpenic compounds was mainly observed using molecular dereplication techniques using Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). Subsequently, the plant material was subjected to the chromatographic fractionation process, obtaining seven sesquiterpenes with related structures, two of the driman type - polygodial (1) and 9-deoxymuzygadial (2), five with a bisabolane skeleton: 3,6-Epidioxy -1,10-bisaboladiene (3a /3b); (R)-6-hydroxy-6-methyl-3-[(S)-6-methylhept-5-en-2-yl]cyclohex-2-enone (4a /4b); 1-methyl-4-(6-methylhept-5-en-2-yl)cyclohex-3-ene-1,2-diol (5a/5b) which are found in a diastereomeric mixture, a-curcumene (6) and a sabinene skeleton: 7-epi-trans-sesquisabinene (7), whose structures were characterized by one- and two-dimensional NMR analyses. This is the first isolation report on the isolation of compounds 2 to 7 in the species D. brasiliensis. The result obtained demonstrated that the diastereomeric mixture of compounds 3a/3b subjected to in vivo evaluation in mice, resulted in a 62% reduction in the parasitic load in adult worms, 98% in the parasitic load of immature eggs in the intestine and a 99% reduction in oviposition in feces of the animal model. Therefore, it was possible to observe that the potential anti-S. mansoni from the mixture of compounds 3a/3b are promising for a possible molecular prototype in the treatment of schistosomiasis