Preliminary study of the anti-inflammatory activity of hexane extract and fractions from Bursera simaruba (Linneo) Sarg. (Burseraceae) leaves.

Bursera simaruba (L.) Sarg. leaves hexane extracts display anti-inflammatory activity on the adjuvant-carrageenan-induced inflammation in rats. In order to isolate and identify the active compounds of the hexane extract, we performed a preliminary phytochemical study and a bioassay-directed fractionation using the carrageenan-induced paw oedema test in mice. From the nine fractions (A-I) obtained, of an initial chromatographic separation, fractions A and E (doses equivalents to 1.50 g dry plant/kg body weight) showed the strongest anti-inflammatory activity comparable to that of the reference drug phenylbutazone (80 mg/kg). The isolation and characterization of 3-methylene-7,11,15-trimethylhexadec-1-ene (neophytadiene) (1), ergost-5-en-3beta-ol (2), 24S-stigmast-5,22E-dien-3beta-ol (3), 24S-stigmast-5-en-3beta-ol (4) and alpha-amyrin (5), from these fractions is reported.

A new coumarin from the fruits of Coutarea hexandra.

A new 5-O-beta-D-glucopyranosyl-4-(4-hydroxyphenyl)-7-methoxy-2H-chromen-2-one (1), together with four known compounds, one coumarin, 5-O-beta-D-galactopyranosyl-4-(4-hydroxyphenyl)-7-methoxy-2H-chromen-2-one (2) and three cucurbitacins, 23,24-dihydrocucurbitacin F (3), 23,24-dihydro-25-acetylcucurbitacin F (4) and 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F (5) have been isolated and characterised from the ethanol extract of Coutarea hexandra fruits. Their structures have been established by spectroscopic analysis (NMR and MS). Interpretation of the HMQC, HMBC, COSY-45 and NOESY experiments permitted us to establish stereochemistry of the natural products. All compounds were tested in cytotoxicity assays against the breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines.

Analgesic-antiinflammatory properties of Proustia pyrifolia.

The antiinflammatory (per os and topic) and analgesic (per os) properties of the aerial part of Proustia pyrifolia a species in danger of extinction were investigated, and the major compounds of two of its active extracts were isolated. In addition, the evaluation of cytotoxicity in three tumoral cell lines and the acute toxicity of the crude methanol extract were also assayed, together with the antioxidant activity for the different extracts of this species. The results of the evaluation of the topic antiinflammatory activities induced by arachidonic acid, and phorbol 12-myristate 13-acetate of the different extracts showed that this species possesses active constituents that could diminish cyclo-oxygenase and lipoxygenases activities, the enzymes that allow the synthesis of proinflammatory endogenous substances as prostaglandin E(2) and leukotrienes, respectively. Our results corroborate the antiinflammatory and analgesic effects of Proustia pyrifolia, and could justify its use in folk medicine for the treatment of rheumatic and gout illnesses. From bio-active extracts beta-sitosterol, quercetin and dihydroquercetin were obtained, and these compounds could explain in part the antiinflammatory, analgesic and antioxidant activities of this species. The crude methanol extract did not present acute toxicity or cytotoxic activity, however only this extract exhibited antioxidant activity.

Anti-inflammatory activity of leaf extract and fractions of Bursera simaruba (L.) Sarg (Burseraceae).

Seeking for new medicinal compounds in plants used in traditional medicine, which grow in Venezuela, we investigated the anti-inflammatory activity of the leaf hexane extract (HE) and several fractions obtained from sp. Bursera simaruba (L.) Sarg. (Indio desnudo) using carrageenan-induced paw edema inflammation. Oral administration of leaf HE as well I (91-100) fraction, and compounds VIII 25-26 and VIII 29, inhibited the carrageenan-induced paw edema with different capacity and time course, over a period of 7h. The anti-inflammatory effect was comparable to that of the reference drug phenylbutazone (80 mg/kg, p.o.). Included in fraction I (91-100), Vitamin E was identified as one of its components and compound VIII 29 was identified as a methyl-beta-peltatin A. The comparison of the anti-inflammatory activity of VIII 29 fraction with the corresponding standard of methyl-beta-peltatin A, suggest that this compound could be one of the active principles involved in the anti-inflammatory activity of Bursera simaruba (L.) Sarg. leave. Our results contribute to the pharmacological support of the use of Bursera simaruba (L.) Sarg. as anti-inflammatory in the ethnomedicinal practice.

A new cucurbitacin glycoside from Kageneckia oblonga (Rosaceae).

A novel cucurbitacin glycoside has been isolated from aerial parts of Kageneckia oblonga R. et P. and shown to be 3beta-(beta-D-glucosyloxy)-16alpha,23alpha-epoxycuc urbita-5,24-dien-11-one. The structure was established by usual spectroscopic and two-dimensional (2D) NMR techniques. This compound has found to be nontoxic when tested in-vivo cell culture assays. In previous investigations we reported 23,24-dihydrocucurbitacin F and prunasine. This was the first report on cucurbitacins from the genus Kageneckia (Rosaceae).

Bioactive phenolic derivatives from Acaena splendens methanol extract.

Acaena splendens H. et A. has been used in Chilean folk medicine for the treatment of fever and inflammation. A description of the in vivo reduction of bacterial pyrogen-induced fever in rabbits and carrageenan-induced paw oedema in guinea pigs is presented. The methanol extract named ME-1, obtained after succesive extractions with petroleum ether and dichloromethane, showed a strong antipyretic action (45.7% of effect), though the antiinflammatory activity was only observed after submitting this extract to column fractionation, giving a crude mixture of flavonoids named C4 with both activities (55.7% and 98.9% of antiinflammatory and antipyretic effect respectively at a dose of 600 mg/kg). The bioassay-guided fractionation by column chromatography afforded the active fraction, which contained (-,-)-epicatechin, tiliroside, 7-O-acetyl-3-O-beta-D-glucosyl-kaempferol and 7-beta-D-glucosyloxy-5-hydroxy-chromone.

Synthesis and cytotoxicity of hydrophobic esters of podophyllotoxins.

Diverse norbornenecarboxylate esters of podophyllotoxin and its epimers and diastereoisomers have been prepared through Diels-Alder cycloaddition by treating the dienophilic acrylates of cyclolignans with cyclopentadiene. Their cytotoxicities against several cancer cell lines have been evaluated and the results compared with those found for other lignan esters. Podophyllotoxin adducts showed a one-fold increase in activity when compared to the natural product. The preparation of more hydrophobic esters, which showed less cytotoxicity, demonstrated that this activity is not primarily due to the lipophilic factor, but mainly to the spatial arrangement of the bulky moiety, which could contribute to increase the binding to the target site.

Leishmanicidal activity of some stilbenoids and related heterocyclic compounds.

We have evaluated the leishmanicidal activity of some natural and semisynthetic dihydrostilbenoids and several compounds of other series of dihydrostilbamides, isoindoles, phthalazinones, imidazoisoindoles and pyrimidoisoindoles. The evaluation was performed in vitro, on cultures of cutaneous, mucocutaneous and visceral strains of Leishmania spp. The most potent and selective compounds of these series were the dihydrostilbene piperidides.

Anti-Trypanosoma activity of some natural stilbenoids and synthetic related heterocyclic compounds.

We report the anti-Chagasic activity of the natural dihydrostilbenoid isonotholaenic acid and several simple derivatives, as well as that of some representative compounds of related synthetic series, with basic structures of benzalphthalides, dihydrostilbamides, isoindoles, phthalazin-1-ones, imidazo[2,1-a]isoindoles and pyrimido[2,1-a]isoindoles. The evaluation was performed in vitro on cultures of epimastigote and trypomastigote forms of Trypanosoma cruzi. Some of the tested compounds resulted to be as potent as benznidazole (epimastigotes), and others were shown to be more active than gentian violet (trypomastigotes), used as reference drugs.