Acylated cholestane glycosides from the bulbs of Ornithogalum saundersiae

Kubo, Satoshi; Mimaki, Yoshihiro; Terao, Miki; Sashida, Yutaka; Nikaido, Tamotsu; Ohmoto, Taichi

doi:10.1016/s0031-9422(00)97565-4

Cited by 159 publications

(135 citation statements)

References 12 publications

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“…The MALDI tandem mass spectra (MS [2][3][4] ) of biologically active steroids, i.e., OSW-1 (1) and its analogue (2), marinobufotoxin (3) and its homologue (4), were obtained using MALDI-QIT-TOF-MS n . Differences occurred in the molecular-related ion species observed in single stage MS.…”

Section: Discussionmentioning

confidence: 99%

“…In compound 1, this product ion was obtained in both MS 3 ) as a precursor ion was performed, as shown in Fig. 2c.…”

Section: Maldi-qit-tof-msmentioning

confidence: 99%

“…Thus the product ion at m/z 299 of 4 is assumed to originate due to dehydration from the pimeloylarginine ester ion at m/z 317. Based on the results of investigating product ions obtained in MS [2][3] experiments, fragmentation pathways, structures of product ions, and cleavage portions are proposed in Chart 3 and Fig. 4.…”

Section: Maldi-qit-tof-msmentioning

confidence: 99%

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Analyses of Biologically Active Steroids: Antitumor Active OSW-1 and Cardiotonic Marinobufotoxin, by Matrix-Assisted Laser Desorption/Ionization Quadrupole Ion Trap Time-of-Flight Tandem Mass Spectrometry

Kasai

Tsubuki

Shimada

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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) has been used for the identification and structural determination of steroids. Steroidal glycoalkaloids extracted from natural plants are identified using electrospray ionization (ESI) in ion trap (IT) MS,1) and steroid glucuronides are analyzed using a triplequadrupole (Q) instrument with a turbo ion-spray source. 2)An acetylated cholestane diglycoside, OSW-1 (1), (3b,16b,17a-trihydroxycholest-5-en-22- one 16-O-{O-[2-O-(4-methoxybenzoyl)-b -D-xylopyranosyl]-(1→3)-2-O-acetyl-a-L-arabinopyranoside}), was isolated by Sashida and co-workers as the main constituent from the bulbs of Ornithogalum saundersiae (Liliaceae) and found to show potent cytotoxicity against a variety of malignant human tumor cells.3) OSW-1 exhibits low toxicity against normal cells but inhibits the growth of malignant cells and is 10-100-fold more potent than clinically established anticancer agents such as mitomycin C, doxorubicin, camptothecin, and paclitaxel.4) Fuchs and colleagues proposed that the active intermediate might be a 22-oxocarbenium ion, which could be generated from 22-carbonyl and 16a-hydroxy moieties.5) Yu and colleagues have recently reported that both 22-methylene and 23-heteroatom (O, S, NH) analogues of OSW-1 were as potent as the parent natural products against the growth of tumor cells. 6) However, the precise mechanism by which OSW-1 exerts its effects remains unclear. A further study of the structure-activity relationships of OSW-1 analogues having heterocyclic rings, such as thiophene and thiazole, at the side chain was therefore designed. We have succeeded in the syntheses of OSW-1 (1) and one of its analogues, ThOSW-1, (20S,23Z,25Z)-3b ,16b ,17a -trihydroxy-23,26-epithiocholesta-5,23,25-trien-22-one 16In a previous study, we investigated the optimum LC/MS conditions to obtain useful ions required to identify structures using ESI and atmospheric-pressure chemicalionization (APCI)-QMS. 9)Cardiotonic steroids are classified into two groups based on the type of unsaturated lactone ring substituted at the 17b-position of the steroidal skeleton, i.e., cardenolides with a five-membered lactone ring and bufadienolides with a sixmembered lactone ring, respectively. Toad steroids isolated from Bufo sp. have a six-membered lactone ring and are divided into two groups according to the form at the 3b-position of the steroid: bufogenin as an unconjugated steroid; and bufotoxin as a steroid conjugate. From ancient times, the skin secretions of native toads, known as ch'an su in China and as senso in Japan, have been employed as cardiac or diuretic agents, and the main cardiotonic constituent in toad venom has been elucidated to be bufotoxin. 10) Marinobufotoxin (3) with a suberoylarginine ester at the 3b-position is one of the main cardiotonic constituents. In addition to this, homologues with other dicarboxylic acids, i.e., pimeric acid, succinic acid, or adipic acid, and analogues with other amino acids, i.e., histidine or glutamine, are known to occur. In addition, other conjugate forms, i.e., sulfates or glucuronides, are...

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Section: Discussionmentioning

confidence: 99%

“…In compound 1, this product ion was obtained in both MS 3 ) as a precursor ion was performed, as shown in Fig. 2c.…”

Section: Maldi-qit-tof-msmentioning

confidence: 99%

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Analyses of Biologically Active Steroids: Antitumor Active OSW-1 and Cardiotonic Marinobufotoxin, by Matrix-Assisted Laser Desorption/Ionization Quadrupole Ion Trap Time-of-Flight Tandem Mass Spectrometry

Kasai

Tsubuki

Shimada

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…3,63 Saponin OSW-1 (1) 64,65 ( Fig. 1), is the major component of a small group of cholestane saponins isolated recently by Sashida et al from the bulbs of Ornithogalum saundersiae, 66 a species of the lily family without any folkloric medicinal background.…”

Section: Bioactivity Of Saponinsmentioning

confidence: 99%

ESI‐QqTOF‐MS/MS and APCI‐IT‐MS/MS analysis of steroid saponins from the rhizomes of Dioscorea panthaica

Zhou

et al. 2006

J. Mass Spectrom.

103

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“…As a new member of cholestane saponin family, OSW-1 was first isolated from the bulbs of Ornithogalum saudersiae (Kubo et al, 1992). Its total chemical synthesis was subsequently accomplished (Deng et al, 1999).…”

mentioning

confidence: 99%

Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2

Zhu

Xiong²,

Yu³

et al. 2005

Mol Pharmacol

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OSW-1 is a new member of cholestane saponin family, which is cytotoxic against several types of malignant cells. We reported herein that OSW-1 induced apoptosis of mammalian cells in a concentration-and time-dependent manner. The drug-induced apoptosis was mediated through the mitochondrial pathway, involving the cleavage of Bcl-2. This drug-induced Bcl-2 cleavage in Chinese hamster ovary (CHO) cells could be suppressed either by dominant-negative caspase-8 or by a caspase-8 inhibitor, suggesting that the Bcl-2 cleavage is dependent on caspase-8. In contrast, the Bcl-2 cleavage was independent of caspase-3 activity. The inhibition of caspase-8 activity also resulted in the reduction of apoptotic cells, indicating that Bcl-2 cleavage induced by caspase-8 promotes the progression of apoptosis. The involvement of the caspase-8 activity in the processes of the OSW-1-induced apoptosis was further examined by using caspase-8-deficient Jurkat T cells. It was found that the caspase-8-deficient cells were resistant to OSW-1-induced Bcl-2 cleavage or apoptosis. Furthermore, the small subunit of caspase-8 was found to interact with Bcl-2 as determined by yeast two-hybrid and coimmunoprecipitation assays. Overexpression of caspase-8 small subunit reduced the cleavage of Bcl-2 and inhibited the apoptosis induced by OSW-1. Taken together, these results demonstrate that OSW-1 is capable of inducing apoptosis in mammalian cells, in which the caspase-8-dependent cleavage of Bcl-2 plays an important role.Saponins belong to a family of glycoconjugtes with a broad spectrum of biological and pharmacological activities (Hostettmann and Marson, 1995). As a new member of cholestane saponin family, OSW-1 was first isolated from the bulbs of Ornithogalum saudersiae (Kubo et al., 1992). Its total chemical synthesis was subsequently accomplished (Deng et al., 1999). It has been reported that OSW-1 was cytotoxic against several types of malignant cells at nanomolar concentrations, which are approximately 10 to 100 times more potent than those of the clinically applied anticancer agents mitomycin C and doxorubicin (Mimaki et al., 1997). Despite its highly potent antitumor activity and unique chemical structure, the molecular basis of its mechanism of action has remained elusive.Apoptosis is a universal cellular process that plays an important role in normal development as well as pathology of a number of human diseases. The resistance to apoptosis is a general feature of cancer cells. Two main pathways are involved in apoptosis. The extrinsic apoptotic pathway is activated by the ligation of death receptors, whereas the intrinsic apoptotic pathway is mediated through mitochondria (Zimmermann et al., 2001). The death receptors, such as Fas, recruit the adaptor protein FADD, which in turn recruits the proform of caspase-8. Aggregation of procaspase-8 leads to its auto-activation and subsequent activation of executioner caspases (Thorburn, 2004). The apoptotic signal can also be amplified through the mitochondria by altering its membra...

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Acylated cholestane glycosides from the bulbs of Ornithogalum saundersiae

Cited by 159 publications

References 12 publications

Analyses of Biologically Active Steroids: Antitumor Active OSW-1 and Cardiotonic Marinobufotoxin, by Matrix-Assisted Laser Desorption/Ionization Quadrupole Ion Trap Time-of-Flight Tandem Mass Spectrometry

Analyses of Biologically Active Steroids: Antitumor Active OSW-1 and Cardiotonic Marinobufotoxin, by Matrix-Assisted Laser Desorption/Ionization Quadrupole Ion Trap Time-of-Flight Tandem Mass Spectrometry

ESI‐QqTOF‐MS/MS and APCI‐IT‐MS/MS analysis of steroid saponins from the rhizomes of Dioscorea panthaica

Apoptosis Induced by a New Member of Saponin Family Is Mediated through Caspase-8-Dependent Cleavage of Bcl-2

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