RESUMO
BACKGROUND: Cytotoxic activity of saponins and phenolic compounds have been described in the literature, but no reports were found on their multidrug resistance (MDR)-modulating effects on human mdr1 gene-transfected mouse lymphoma cell line. MATERIALS AND METHODS: Methylprototribestin, structurally related compounds and a mixture of 3 acetylated isomers of methylprotodioscin were investigated for antiproliferative effect and modulation of drug accumulation. RESULTS: The growth inhibitory dose (ID50) of the compounds ranged from 12.64 to 20.62 mug/ml. Methylprototribestin was the most effective resistance modifier. However, methylprotodioscin, pseudoprotodioscin, prosapogenin A of dioscin, tribestin and 5-O-caffeoylshikimic acid showed moderate MDR reversal activity. In a checkerboard method, methyloprototribestin and the mixture of the 3 acetylated isomers enhanced the antiproliferative effects on MDR cells in combination with doxorubicin. CONCLUSION: Based on these results, methylprototribestin and the mixture of the 3 acetylated isomers can be recommended for further in vivo experiments in combination with anthracyclines in human MDR-cancer xenograft transplanted mice.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Smilax/química , Tribulus/química , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Linfoma de Células T , Camundongos , Fenóis/química , Extratos Vegetais/química , Saponinas/química , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
From the n-butanol soluble fraction of the methanol extract of the rhizomes of Smilax excelsa, three new furostanol saponins 3-O-[4-O-acetyl-alpha-L-rhamnopyranosyl-(1 --> 2)-{alpha-L-rhamnopyranosyl-(1 --> 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol (1), 3-O-[2-O-acetyl-alpha-L-rhamnopyranosyl-(1 --> 2)-{alpha-L-rhamnopyranosyl-(1 --> 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol (2), 3-O-[3-O-acetyl-alpha-L-rhamnopyranosyl-(1 --> 2)-{alpha-L-rhamnopyranosyl-(1 --> 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol (3), and three known saponins: protodioscin (4), pseudoprotodioscin (5) and dioscin (6) were isolated.
Assuntos
Rizoma/química , Saponinas/isolamento & purificação , Smilax/química , Esteroides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Saponinas/química , Esteroides/químicaRESUMO
The steroidal saponins of Tribulus terrestris L. (Zygophyllaceae) are considered to be the factor responsible for biological activity of products derived from this plant. The activity depends on the concentration and the composition of active saponins, which in turn is influenced by the geographical origin of plant material. Samples of T. terrestris collected in Bulgaria, Greece, Serbia, Macedonia, Turkey, Georgia, Iran, Vietnam and India were analyzed by LC-ESI/MS/MS for the presence and the concentration of protodioscin (1), prototribestin (2), pseudoprotodioscin (3), dioscin (4), tribestin (5) and tribulosin (6). The flavonoid rutin (7) was also included in the comparison. The results revealed distinct differences in the content of these compounds depending on region of sample collection, plant part studied and stage of plant development. The samples from Bulgaria, Turkey, Greece, Serbia, Macedonia, Georgia and Iran exhibited similar chemical profile and only some quantitative difference in the content of 1-7 with protodioscin (1) and prototribestin (2) as main components. The Vietnamese and Indian samples exhibit totally different chemical profile. They lack 2 and 5, while tribulosin (6) is present in high amounts. Compounds different from 1 to 7 are dominating in these 3 samples. The presented results suggested the existence of one chemotype common to the East South European and West Asian regions. Most probably, the Vietnamese and Indian samples belong to other chemotypes which are still to be studied and characterized. No clear correlation between the burrs morphology and the chemical composition of the samples has been found.
Assuntos
Geografia , Saponinas/análise , Saponinas/química , Esteroides/química , Tribulus/química , Ásia Ocidental , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Europa (Continente) , Componentes Aéreos da Planta/química , Espectrometria de Massas por Ionização por Electrospray , Esteroides/análiseRESUMO
The known furostanol saponins methylprotodioscin and protodioscin and two new sulfated saponins, sodium salt of 26-O-beta-glucopyranosyl-22alpha-methoxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (methylprototribestin) and sodium salt of 26-O-beta-glucopyranosyl-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (prototribestin) have been isolated from the aerial parts of Tribulus terrestris L. growing in Bulgaria. The structures of the new compounds were elucidated on the basis of 1D and 2D (DQF-COSY, TOCSY, HSQC-TOCSY, HSQC, HMBC, ROESY) NMR data, ESI mass spectra and chemical transformation.
