Estudo químico de Sinningia allagophylla guiado por testes de atividade antiproliferativa

Abstract

Recebido em 18/9/11; aceito em 5/12/11; publicado na web em 28/2/12 CHEMICAL STUDY OF Sinningia allagophylla GUIDED BY ANTIPROLIFERATIVE ACTIVITY ASSAYS. Activity guided fractionation of Sinningia allagophylla (Mart.) Wiehler ethanolic extract yielded a new benzochromene 8-methoxylapachenol, besides seven known compounds: lapachenol, sitosteryl oleate, sitosteryl linoleate, stigmasteryl oleate, stigmasteryl linoleate, dunniol and tectoquinone. Extract, fractions, and compounds lapachenol, 8-methoxylapachenol, and dunniol were tested in vitro against human cancer cell lines U251 (glioma, CNS), MCF-7 (breast), NCI-ADR/RES (drug-resistant ovarian), 786-0 (kidney), NCI-H460 (lung, no small cells), PC-3 (prostate), OVCAR-3 (ovarian), HT-29 (colon), K562 (leukemia) and against VERO, a normal cell line. The most active compound was dunniol, which inhibited the growth of U251, MCF-7, NCI-ADR/RES, OVCAR-3 and K562 cell lines.Keywords: Sinningia allagophylla; Gesneriaceae; antiproliferative activity. INTRODUÇÃOSinningia (Gesneriaceae) é um gênero de plantas ornamentais encontrado nas regiões tropicais do Novo Mundo. Atualmente são reconhecidas 68 espécies, a maioria ocorrendo em território brasileiro.1 Sinningia allagophylla (Mart.) Wiehler é uma erva anual, de tubérculo perene, largamente espalhada no Brasil (rgiões centro-oeste, sul e sudeste), Argentina, Paraguai e Uruguai.2 É conhecida como batata-do-campo ou batata-de-perdiz, sendo empregada na medicina popular como febrífugo, diurético, depurativo, emoliente e tônico. O câncer é uma doença com elevado índice de mortalidade, que atinge anualmente milhões de pessoas ao redor do mundo. Embora tenha havido muito progresso na quimioterapia do câncer, muitos tumores ainda são de difícil remissão, tornando necessária a procura de novos agentes antitumorais. As plantas superiores constituem uma rica fonte de novas substâncias, que podem ser úteis contra neoplasias.8 Como parte de um projeto que visa a procura de substâncias com atividade citotóxica de plantas brasileiras, foi realizado o estudo fitoquímico de S. allagophylla guiado por ensaios de atividade antiproliferativa contra linhagens de células tumorais humanas. RESULTADOS E DISCUSSÃOO extrato etanólico dos tubérculos de S. allagophylla foi testado contra oito linhagens de células tumorais, apresentando um fraco efeito antiproliferativo in vitro, exceto para a linhagem de células K-562 (leucemia), que teve o seu crescimento totalmente inibido com uma concentração (TGI) de 5,13 µg mL -1 (Tabela 1). Por essa razão, esse extrato foi submetido à partição com hexano, diclorometano, acetato de etila e 1-butanol e as respectivas frações foram avaliadas frente a células tumorais e uma linhagem de células normais (VERO). A maior atividade foi observada na fração em hexano, a qual inibiu o crescimento de seis linhagens de células tumorais, com valores de TGI variando entre 15,5-32,7 µg mL -1 , mas foi inativa frente à linhagem VERO (células normais, TGI > 250 µg mL -1 ). Pôde ser notado que a linhagem K562 foi menos susceptíve...

Naphthochromenes and Related Constituents from the Tubers of Sinningia allagophylla

“…Two olefinic protons (δ H 5.65, 6.55), one methoxy group (δ H 3.96), one hydroxymethylene group (δ H 3.70, 3.78), and one methyl group (δ H 1.42) were also observed. These data were very similar to those of lapachenole, reported from S. allagophylla 4 and reisolated in this work. In comparison with lapachenole, compound 1 differs by replacement of one methyl group at C-2 by a hydroxymethylene group.…”

“…The 1 H NMR data of 3 (Table 2) showed signals for six aromatic protons in the spin systems of two 1,2,4trisubstituted aromatic moieties (δ H 7.13−8.13), three isolated protons (δ H 6.09, 6.36, and 6.58), four methoxy groups (δ H 3.82, 3.87, 3.93, and 3.94), four methyl groups (δ H 1.31, 1.55, 1.62, and 1.70), two diastereotopic methylene protons (δ H 1.99 and 2.22), and a benzylic proton (δ H 3.77). These data resembled those of 8-methoxylapachenole, 4 but the molecular mass and the duplication of several signals indicated a dimeric structure. The presence of benzylic and methylene protons suggested hydrogenation of an olefinic bond of the 2H-pyran ring.…”

“…The naphthoquinone dunniol was the compound responsible for the cytotoxic activity observed in the ethanolic extract. 4 Another study showed that the ethanolic extract, its hexanes-soluble fraction, and the major compound of this fraction, 8-methoxylapachenole, showed anti-inflammatory and antinociceptive activities. 5 The present work reports the isolation and identification of several compounds from the noncytotoxic CH 2 Cl 2 -soluble fraction of the ethanolic extract (DCMS) of S. allagophylla tubers.Successive chromatographic fractionation of the DCMS fraction yielded five new (1−5) and 13 known compounds.…”

Chemical Composition and Antiproliferative Activity of the Ethanolic Extract of Cyperus articulatus L. (Cyperaceae)

“…Our results resemble the study of Mazzio et al [34], which demonstrated that ethanolic extract of rhizomes of C. rotundus showed moderate anticancer activity in Neuro-2a cells (LC50 = 2.528 to 4.939 mg/mL calculated from dose-dependent cell death). Riva [35] tested the ethanolic extract of tubers of S. allagophylla against eight tumor cell lines, which presented a weak in vitro antiproliferative effect, except for the line of K-562 cells (leukemia), whose growth was completely inhibited with TGI concentration of 5.13 µg/mL (Figure 3). In summary, the major compounds identified in EECA belong to the sesquiterpenes group (e.g., isocorimbolone and mustakone) and demonstrated significant anti-proliferative activity against the tumor cell lines tested.…”

Naphthoquinones of Sinningia reitzii and Anti-inflammatory/Antinociceptive Activities of 8-Hydroxydehydrodunnione

“…We are investigating this genus as part of a project of screening Brazilian Gesneriads, aiming at the isolation of new bioactive compounds. In previous studies we reported the isolation of cytotoxic and anti-inflammatory compounds from Sinningia allagophylla, 8,9 as well as cytotoxic and antinociceptive compounds from S. aggregatta. 10,11 Recently, a bioassay-guided fractionation led to the isolation of 7hydroxy-6-methoxy-α-dunnione, a naphthoquinone with antiinflammatory and antipyretic properties, from the less polar extracts of S. canescens tubers.…”