Contribuição ao estudo fitoquímico do gênero Strychnos da flora amazônica

Abstract

The genus Strychnos, the principal genus of the Loganiaceae family, is natural of tropical regions and comprises about 200 species. Besides being used to make "curare" (arrow poison obtained from vegetal sources prepared by some Amazonian Indian tribes), this genus has history in folk medicine, being registered for the American species, antimalarial, tonic, aphrodisiac, febrifuge, and antianaemic effects. The most studied pharmacological actions are the convulsants and relaxants. However, more recent studies have revealed some new structures that present antimitotic, cytotoxic, antimicrobial, antitumoral, amoebicide, hypotensive, antipaludism activities, etc. In this thesis, besides a bibliographic survey of phytogeographical, botanical, ethnopharmacological, chemical and pharmacological aspects of genus Strychnos in South America, a bank of data with accumulated information found in the literature was elaborated, chemosystematic studies about Strychnos sections were carried out, and phytochemical studies about the S.cogens, S.guianensis and S.mattogrossensis species were accomplished. The phytochemical investigations of the selected species allowed the isolation and identification of the following substances: lupeol (triterpene) and longicaudatine (alkaloid) of S.cogens; harmane (alkaloid), olivil, cicloolivil and cicloolivil carbonate (lignans), palmitic,oleic, estearic and nonadecanoic acids ( fatty acids) of S.guianensis; strycimobrasiline,12-hydroxy-11-methoxystrychnobrasiline,12-hydroxy-10,11- dimethoxystrychnobrasiline (alkaloids), campesterol, sito sterol, stigmasterol (steroids), palmitic,linoleic, oleic, esteasic and behenic acids (fatty acids) of S.mattogrossensis. The analyses involved conventional chemical route for alkaloid isolation, as well as chromathogaphic methods and espectrometric (ESI, HMQC, HMBC, etc) modem techniques. RivIN spectra of strychnobrasiline were accomplished at three temperatures, being registered RMN 111 and RMN13 C spectra of two rotamers, at 298° (ambient temperature) and 288° K, whereas the signal coalescences of the two rotamers at 308° K were observed. The 12-hydroxy-10, 11-dimethoxystrychnobrasiline and the cicloolivil carbonate are unknown as natural products, although the latter could be formed during the chemical procedure used. Strychnobrasiline is devoid of intrinsic antimalarial effect, but it exhibits significant CQ-potentianting actions, reverting the chloroquine resistance in Plasmodium falciparum . Longicaudatine has a reserpine-like activity. For the steroids (sitosterol and stigmasterol) and triterpene lupeol, common in plants, analgesic and immunosuppression actions, respectively, are remarkable. Olivil and cicloolivil present antioxidant action, usually associated to anticancer activity. Cicloolivil carbonate exhibited no significant inhibitory activity against neuroblastoma in mice, in preliminary tests carried out at FIOCRUZ , Rio de Janeiro. This occurrence of lignans represents the first register in American Strychnos species. Phytochemical studies confirmed the genus Strychnos as a promising alkaloid source, and also revealed it as a new lignan source. The pharmacological potentiality of the lignoids and the large yield of lupeol (-1,0%) obtained from the root barks extracts of Strychnos cogens justify a more intensive investigation of the nonalkaloidal content of these plants, maybe responsible for many activities attributed to taxon by the folk medicine.