Furostanol Saponins Research Articles

The cytotoxicity of protoneodioscin (NSC-698789), a furostanol saponin from the rhizomes of Dioscorea collettii var. hypoglauca, against human cancer cells in vitro.

Protoneodioscin (NSC-698789) is a furostanol saponin isolated from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for cancer treatment. Our studies showed that protoneodioscin is cytotoxic against most cell lines from leukemia and solid tumors in the NCI's (National Cancer Institute, USA) anticancer drug screen. Leukemia, CNS cancer, and prostate cancer are the most sensitive subpanels to protoneodioscin, while melanoma, ovarian cancer, and renal cancer are less sensitive. The preliminary animal studies showed that the maximum tolerant dose of protoneodioscin was 600 mg/kg to mice. Based on an analysis of the COMPARE software with protoneodioscin as a seed compound, no compounds in the NCI's database have similar cytotoxicity patterns to those of protoneodioscin, indicating a potentially novel mechanism of anticancer action involved.

Methyl protogracillin (NSC-698792): the spectrum of cytotoxicity against 60 human cancer cell lines in the National Cancer Institute's anticancer drug screen panel.

Methyl protogracillin (NSC-698792) was a furostanol saponin isolated from the rhizome of Dioscorea collettii var. hypoglauca (Dioscoreaceae), a Chinese herbal remedy for the treatment of cervical carcinoma, carcinoma of urinary bladder and renal tumor for centuries, in our previous studies. In order to systematically evaluate its potential anticancer activity, methyl protogracillin was tested for its cytotoxicity in vitro against 60 human cancer cell lines in the National Cancer Institute (NCI)'s anticancer drug screen. As a result, it was found that methyl protogracillin was cytotoxic against all the tested cell lines from leukemia and solid tumors in the NCI's human cancer panel; it showed particular selectivity against one colon cancer line (KM12), one central nervous system (CNS) cancer line (U251), two melanoma lines (MALME-3M and M14), two renal cancer lines (786-0 and UO-31) and one breast cancer line (MDA-MB-231) with GI50< or =2.0 microM. The selectivity between these seven most sensitive lines and the least sensitive line (CCRF-CEM) ranged from 26- to 56-fold. In the same cancer subpanel, selectivity more than 15-fold was observed between MDA-MB-231 and MCF-7, NCI-ADR-RES, BT-549 in breast cancer. From a general view of the mean graph, CNS cancer is the most sensitive subpanel, while ovarian cancer and renal cancer are the least sensitive subpanels. Based on an analysis of the COMPARE computer program with methyl protogracillin as a seed compound, no compounds in the NCI's anticancer drug screen database have similar cytotoxicity patterns (mean graph) to that of methyl protogracillin, indicating a potential novel mechanism of the anticancer action involved.

New spirostanol steroids and steroidal saponins from roots and rhizomes of Dracaena angustifolia and their antiproliferative activity.

The MeOH extract of Nam ginseng (roots and rhizomes of Dracaena angustifolia) afforded nine new compounds, including three spirostanol sapogenins, named namogenins A-C (1-3), four spirostanol saponins, named namonins A-D (4-7), a furostanol saponin, named namonin E (8), and a pregnan glycoside, named namonin F (9), along with another eight known steroidal saponins (10-17). Their structures were determined on the basis of spectral analyses and chemical methods. All compounds were tested for their antiproliferative activity against murine colon 26-L5 carcinoma, human HT-1080 fibrosarcoma, and B-16 BL6 melanoma cells. Compounds 4, 5, and 10 showed potent antiproliferative activity against HT-1080 fibrosarcoma cells, having IC(50) values of 0.2, 0.3, and 0.6 microM, respectively, comparable to that of doxorubicin.

MOLLUSCICIDAL STEROIDAL SAPONINS FROM YUCCA ELEPHANTIPES

Three spirostanol and two furostanol saponins have been isolated from the methanol extract of the leaves of Yucca elephantipes .The structures of these saponins were established as 3-O-β -D-xylopyranosyl-(1→2)- B-D- glucopyranosyl-(1→3)- β-D-glucopyranoside D- galactopyranoside yamogenin (I),3-O-β-D-xylopyranosyl-(1-→2)[ -β-D- glucopyranosyl-( 1-3 )] , 26-B-D- glucopyranoside (25 S) -furost- 5-ene-3,22,26 -triol (II), 3- O- α -L -rhamnopyranosyl- ( 1→2 )-[ β- D-xylopyranosyl- (1-→3) -β-D-glucopyranosyl-(1–>4)- β-D-galactopyranoside gitogenin (III), 3-O-β-D-xylopyranosyl- ( 1→ 3)- [β-D-glucopyranosyl -(1→2) - s-D-glucopyranosyl-(1→4)- β- D-galactopyranoside gitogenin (IV),and 26-0-β-D-glucopyranosyl-22-0-methyl (25R)-5-furostan -2,3,26-tetrol-3-O-[α-L-rhamnopyranosyl -(1->3)]- s -D-glucopyranosyl -(1->2)- β-D-glucopyranosyl-(1-4)- β-D- galactopyranoside (V). Saponins I, III and IV showed high molluscicidal activities against Biomphalaria alexandrina snails after 24 hours exposure (LC90 = 4,9 and 7 ppm ) whereas saponins II and V were inactive up to 50 ppm

Two novel furostanol saponins from the rhizomes of Dioscorea panthaica Prain et Burkill and their cytotoxic activity

Dioscoresides A and B were isolated from the rhizomes of Dioscorea panthaica and shown to possess a novel furostanol skeleton. Their structures were fully elucidated as 3- O-[β- d-glucopyranosyl-(1→3)- O-α- l-rhamnopyranosyl-(1→2)-β- d-glucopyranosyl]-26- O-β-20, 22- seco- d-glucopyranosyl-25 ( R)-furosta-5-en-20, 22-dione-3β, 26-diol and 3- O-[bis-α- l-rhamnopyranosyl-(1→4 and 1→2)-β- d-glucopyranosyl]-26- O-β- d-glucopyranosyl-20, 22- seco-25 ( R)-furosta-5-en-20, 22-dione-3β, 23( S), 26-triol by spectroscopic techniques and chemical means. These compounds exhibited cytotoxic activity tested in vitro on A375-S2, L929 and Hela cell lines.

Steroidal glycosides from the bulbs of Camassia leichtlinii and their cytotoxic activities.

Phytochemical analysis of the bulbs of Camassia leichtlinii (Liliaceae) resulted in the isolation of six new spirostanol saponins, a new furostanol saponin, a cholestane glucoside, and four known steroidal saponins. The structures of the new saponins were determined by detailed analysis of their spectral data, including two-dimensional NMR spectroscopy, and by the results of hydrolytic cleavage. Cytotoxic activities of the isolated compounds against human oral squamous cell carcinoma (HSC-2) cells and normal human gingival fibroblasts (HGF) are also reported.

Steroidal saponins from Dracaena surculosa.

A phytochemical investigation of the whole plant of Dracaena surculosa resulted in the isolation of nine steroidal saponins, including three new bisdesmosidic spirostanol saponins, named surculosides A (1), B (2), and C (3), and a new bisdesmosidic furostanol saponin (4), which are based on (25S)-spirost-5-ene-1beta, 3beta-diol [(25S)-ruscogenin] as the aglycon. The structures of 1-4 were determined by spectroscopic analysis, including 2D NMR spectroscopic data, and the results of hydrolytic cleavage. The isolated saponins were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells.

Steroidal oligoglycosides from the seeds of Allium tuberosum.

Three new spirostanol steroidal oligoglycosides, together with a known oligoglycoside, were obtained from the seeds of Allium tuberosum after enzymatic hydrolysis of furostanol saponin fraction by beta-glucosidase. On the basis of spectroscopic analysis, the structure of new spirostanol oligoglycosides were elucidated as (25S)-spirost-5-ene-2alpha,3beta-diol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L-rhamnopyranosyl-(1-->2)]-be ta-D-glucopyranoside, (25S)-spirostane-3beta,5beta,6alpha-triol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside, and (25S)-5beta-spirostane-3beta,6alpha-diol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside.

Furostanol saponins from Allium tuberosum

Three new furostanol saponins, tuberoside A, B and C, have been isolated from the seeds of Allium tuberosum. On the basis of chemical reactions and spectral data, their structures were established as 26- O-β- d-glucopyranosyl-(25 S)-5α-furost-20(22)-ene-2α,3β,26-triol 3- O-α-L-rhamnopyranosyl-(1→2)- O-β- d-glucopyranoside; 26- O-β- d-glucopyranosyl-(25 S)-5α-furost-20(22)-ene-2α,3β,26-triol 3- O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-β- d-glucopyranoside and 26- O-β- d-glucopyranosyl-(25 S)-5α-furost-20(22)-ene-2α,3β,26-triol 3- O-α-L-rhamnopyranosyl-(1→2)-[β- d-glucopyranosyl-(1→3)]-β- d-glucopyranoside, respectively.

Molluscicidal steroidal saponins and lipid content of Agave decipiens

GLC analysis of the petrol extract of the leaves of Agave decipiens revealed that n-hexacosane was the main hydrocarbon, β-sitosterol the main sterol and oleic acid the main fatty acid. Two spirostanol and two furostanol saponins have been isolated from the methanolic extract. The structures of these saponins were established as 3- O-α- l-rhamnopyranosyl-(1→2)-[α- l-rhamnopyranosyl-(1→4)]-β- d-glucopyranosyl-26- O-β- d-glucopyranosyl-22α-methoxy-(25R)-furost-5-ene-3β,26-diol ( 1), neoruscogenin 1- O-β- d-glucopyranosyl-(1→3)-[α- l-rhamnopyranosyl-(1→2)]-β- d-glucopyranosyl-(1→4)-β- d-galactopyranoside ( 2) , 1- O-α- l-rhamnopyranosyl-(1→2)-[α- l-rhamnopyranosyl-(1→4)]-β- d-glucopyranosyl-26- O-β- d-glucopyranosyl-22- O-methylfurosta-5,25(27)–diene-1β,3β,22,26–tetraol ( 3) and neohecogenin 3- O-β- d-glucopyranosyl-(1→3)-[β- d-xylopyranosyl-(1→3)-β- d-xylopyranosyl-(1→2)]–β- d-glucopyranosyl-(1→4)-β- d–galactopyranoside ( 4). Saponins 2 and 4 showed high molluscicidal activity against B. alexandrina snails (LC 90=13 and 6 ppm, respectively), whereas saponins 1 and 3 were inactive up to 50 ppm.

Steroidal saponins from the bulbs of Lilium candidum.

Five new spirostanol saponins and a new furostanol saponin were isolated from the fresh bulbs of Lilium candidum. Their structures were elucidated on the basis of spectroscopic analysis, including two-dimensional NMR spectroscopic techniques and the result of acid hydrolysis. The isolated saponins contained a branched triglycoside moiety assigned as O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->6)]-beta - D-glucopyranose with the formation of an O-glycosidic linkage to C-3 of the aglycone as the common structural feature. The inhibitory activity of the saponins on Na+/K+ ATPase was evaluated.

Steroidal saponins from the bulbs of Allium karataviense.

Chemical examination of the bulbs of Allium karataviense led to the isolation of five new spirostanol saponins (7-11) and a new furostanol saponin (12), together with a known steroidal sapogenin (1) and five known saponins (2-6). The structures of the new saponins were determined by detailed analysis of their spectral data, including two-dimensional NMR spectroscopy. The steroidal saponins produced by A. karataviense, except for 5 and 6, were found to be based upon (25R)-5 alpha-spirostane-2 alpha,3 beta,5,6 beta-tetrol (alliogenin) and contain a beta-D-glucopyranosyl moiety with the formation of an O-glycoside linkage to C-2 of the polyhydroxylated steroidal skeleton as the common structural feature. The isolated compounds were evaluated for cytostatic activity against human promyelocytic leukemia HL-60 cells.

A furostanol saponin from fruits of Balanites aegyptiaca

A new furostanol saponin was isolated from the mesocarp of Balanites aegyptiaca fruits and identified as 26- O- β-d-glucopyranosyl-(25 R)-furost-5-ene-3,22,26-triol3- O-{[ α-l-rhamnopyranosyl-(1 → 2)]-[β-d-xylopyranosyl-(1 → 2)]-β-d-xylopyranosyl-(1 → 2)}-β-d-xylopyranoside (balanitesin).

Steroidal saponins from the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells

Phytochemical examination of the underground parts of Ruscus aculeatus has been undertaken as part of a systematic study of plants of the Liliaceae. Six new spirostanol saponins and five new furostanol saponins were isolated, and their structures were assigned on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and hydrolysis. Ruscogenin diglycoside with three acetyl groups attached to the inner galactosyl moiety and its corresponding 26-glucosyloxyfurostanol saponin showed cytostatic activity on leukemia HL-60 cells.

Steroidal saponins from the stems of Dracaena concinna

A total of thirteen steroidal saponins, including four new furostanol saponins, were isolated from the fresh stems of Dracaena concinna. The structures of new saponins were determined by detailed analysis of their 1H and 13C NMR spectra, hydrolysis, and by comparison of spectral data of known compounds. Two of the new furostanol saponins are unique in structure possessing a 4α-hydroxyl group on the furostanol skeleton.

Steroidal saponins from the leaves of Cordyline stricta

Three new spirostanol saponins and two new furostanol saponins were isolated from the fresh leaves of Cordyline stricta. Their structures were elucidated on the basis of spectroscopic analysis, including various 2D-NMR techniques, hydrolysis, and by comparison of spectral data of known compounds. Two of the isolated saponins contained a new branched triglycoside moiety assigned as O-α- l-rhamnopyranosyl -(1 → 2)-O- [β- d-xylopyranosyl-(1 → 3)]-β- d-xylopyranose with the formation of an O-glycosidic linkage to C-1 of the aglycone.

New steroidal constituents of the underground parts of Ruscus aculeatus and their cytostatic activity on HL-60 cells.

Phytochemical examination of the underground parts of Ruscus aculeatus has led to the isolation of a total of twelve steroidal saponins, including seven new ones. The structures of the new saponins were determined by spectroscopic analysis and chemical evidence. The furostanol saponin, having a diglycoside moiety modified with a (2S,3S)-2-hydroxy-3-methylpentanoic acid group and an acetic acid group, and its corresponding spirostanol saponin exhibited cytostatic activity on leukemia HL-60 cells.

New steroidal constituents from the bulbs of Lilium candidum.

Eight spirostanol saponins, including four new compounds, and two known furostanol saponins were isolated from the fresh bulbs of Lilium candidum. The structures of new compounds were determined to be (25R,26R)-26-methoxyspirost-5-ene-3 beta,17 alpha-diol 3-O-¿O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->4)] -beta-D-glucopyranoside¿, (25R,26R)-26-methoxyspirost-5-ene-3 beta,17 alpha-diol 3-O-¿O-alpha-L-rhamnopyranosyl-(1-->2)-O-[6-O-acetyl-beta-D-glucopyranos yl- (1-->4)]-beta-D-glucopyranoside¿, (25R,26R)-26-methoxyspirost-5-ene-3 beta,17 alpha-diol 3-O-¿O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside¿ and (25S)-spirost-5-ene-3 beta,27-diol 3-O-¿O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O - [beta-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside¿, respectively, on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and the result of hydrolysis. The inhibitory activity of the isolated saponins on Na+/K+ ATPase was evaluated.

Steroidal glucosides from leaves of Cordyline stricta

A phytochemical study on the leaves of Cordyline stricta yielded four new spirostanol saponins, three new furostanol saponins and a new pregnane glucoside. The structures were determined by detailed analysis of their 1H and 13C NMR spectra, acid-catalysed hydrolysis and by comparison with spectral data of known compounds. Each of the isolated steroidal compounds contained a 3α-hydroxyl group bearing a glucose as the common structural feature. © 1997 Elsevier Science Ltd. All rights reserved

Antineoplastic Agents II: Four Furostanol Glycosides from Rhizomes ofDioscorea collettiivar.hypoglauca

During activity-guided fractionations to screen for antineoplastic agents, further studies by means of preparative HPLC led to the isolation of four known furostanol saponins: protoneodioscin, protodioscin, protoneogracillin, protogracillin, along with their corresponding artifacts: methyl protoneodioscin, methyl protodioscin, methyl protoneogracillin, and methyl protogracillin, from the rhizomes of Dioscorea collettii var. hypoglauca. Among them, protoneodioscin, protodioscin, and protoneogracillin are first reported from the title plant. The structures of the compounds were established on the basis of chemical evidence and spectral analysis (1H-NMR, 13C-IMMR, 1H-1H COSY, HMQC, HMBC, and FAB-MS). These eight compounds all caused morphological abnormality of Pyricularia oryzae mycelia. They also showed cytotoxic activities against the cancer cell line of K562 in vitro as antineoplastic agents.