Remijia ferruginea D.C, Jacaranda caroba D.C e Solanum paniculatum L: fitoquímica, atividades biológicas e síntese de derivados dos ácido ursólico e oleanólico.

Abstract

Jacaranda caroba D.C. (Bignoniaceae), Remijia ferruginea D.C. (Rubiaceae) and Solanum paniculatum L. (Solanaceae) are plant species traditionally employed as tonic and bitter, among other uses. The main goals of the present study were to isolate and identify the major micromolecular compounds of these species, to evaluate their biological activities related to the traditional uses and to undertake chemical transformations on triterpenes obtained from the species. Ursolic acid was isolated from the ethanol extracts of J. caroba aerial parts and R. ferruginea stems, along with b-sitosterol, whereas oleanolic acid was obtained from the first and stigmasterol from the second species, being their occurrence in both here described for the first time. The fractionation of the ethanol from S. paniculatum leaves resulted in the new spirostanic saponin _25(27)-tigogenin-3-O-_-D-glucopyranoside (1), identified by spectrometric data as an epimeric mixture at C-22, along withneotigogenin and a mixture of b-sitosterol and stigmasterol. The administration of each extract at the dose of 1.0 mg/kg body weight to rats fed with high-fat diet increased the plasmatic triglycerides in comparison to the control group (p<0.05). Extracts administration at the doses of 0.1 mg/kg body weight increased the lipoprotein lipase activity, as compared to the control group (p<0.05). These results suggest the potential of the species for treating dyspepsia. S. paniculatum is also traditionally used for treating viral infections, including herpes. The ethanol extractfrom its leaves exhibited in vitro antiviral activity against Human Herpes Virus type 1 (EC50 = 428.9 ± 19.2 ìg/mL) and murine Encephalomyocarditis Virus (EC50 = 298.0 ± 11.2 ìg/mL). The saponin 1 presented significant antiherpes (EC50 = 170.8 ± 1.7 ìg/mL) and anti-vaccinia virus effects (EC50 = 177.0 ± 3.3 ìg/mL), with lowcytotoxicity (CC50 > 400 ìg/mL). Ursolic and olenaolic acids, obtained in bulk amounts from J. caroba aerial parts, were submitted to chemical transformations at C-3, C-11 and C-28 positions, resulting in 5 oleanolic derivatives and 21 ursolic derivatives, among them 6 new compounds. The cytotoxic activity of some selected ursolic derivatives was evaluated in vitro against tumor cell lines of breast MDA-MB- 231, colon HT29 and lung A549. A derivative containing hydroxyl groups at C-3 and C-28 was about nine-fold more potent than the parent compound ursolic acid. Someselected ursolic derivatives were assayed in vitro against Plasmodium falciparum and only a compound containing a keto group at C-3 was partially active (IC50 42 ìg/mL).