Total Synthesis and Stereochemical Confirmation of Manassantin A, B, and B<sub>1</sub>

Hanessian, Stephen; Reddy, Gone Jayapal; Chahal, Navjot

doi:10.1021/ol0621710

Cited by 55 publications

(34 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We sought to optimize the structure of manassantin A and explore anti-cancer effects of its derivatives. Using a published method [19], we synthesized manassantin A, its stereoisomers and a series of derivatives (Fig 1A), and determined their HIF-1 inhibitory activities through a cell-based HIF-1 reporter assay [17]. While the change of the tetrahydrofuran configuration (JYJ5802 and JYJ5807) only slightly altered the HIF-1 inhibitory activity (Fig 1A and 1B), the central tetrahydrofuran moiety appears to be important for HIF-1 inhibition as its replacement with other ring moieties or an aliphatic core (XPS1801 and LXY6022) dramatically decreased the HIF-1 inhibitory activity (Fig 1A and 1B).…”

Section: Resultsmentioning

confidence: 99%

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

Lang

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.

show abstract

Section: Resultsmentioning

confidence: 99%

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

Lang

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Activity-guided chromatographic separation of 80% EtOH extract led to isolation of eleven compounds including three active neolignans (1-3), four flavonoids (4-7), and four aristolactams (8)(9)(10)(11). The structures of 1-11 were identified as manassantin A (1), 27,28) manassantin B (2), 29) (−)-saucerneol (3), 29,30) quercetin-3-O-β-Dglucuronopyranoside (4), 31) quercitrin (5), 32) 33) isoquercitrin (7), 34) saurolactam (8), 35) aristolactam AII (9), 36) piperumbellactam B (10), 37) and aristolactam BII (11) 36) by analysis of spectroscopic data including 1 H-and 13 C-NMR data as well as by comparison of their spectroscopic data with the values reported in the literature (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Anti-proliferative Neolignans from <i>Saururus chinensis</i> against Human Cancer Cell Lines

Lee

Kim

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Activity-guided fractionation of an 80% EtOH extract from the aerial parts of Saururus chinensis led to isolation of three anti-proliferative neolignans (1-3) along with four flavonoids (4-7) and four aristolactams (8-11). Their chemical structures were identified by analysis of spectroscopic data. All compounds 1-11 were evaluated for their activities against 28 human cancer cell lines using an in vitro cell proliferation assay. Compounds 1-3 showed potent anti-proliferative activities against cervical (C33a, IC 50 0.01 µM for 1; 0.28 µM for 2; 2.80 µM for 3) and lung (NCI-H460, IC 50 0.05 µM for 1; 1.37 µM for 2; 6.46 µM for 3) cancer cells without any remarkable cytotoxic effects on human normal lung cells as a control. Taken together, these data demonstrated the identification of anti-proliferative neolignans which are active components of S. chinensis.

show abstract

“…Numerous studies have been performed to identify the new molecules. The manassantin group of structurally related and functionally unique dineolignans were recently isolated from active root extracts of Saururus cernuus L (Saururaceae), also referred to as "lizard tail" [11]. This fragrant aquatic plant is found in the North America as well as in many parts of Asia ( Saururus chinensis ) [12-14].…”

Section: Introductionmentioning

confidence: 99%

Effect of manassantin B, a lignan isolated fromSaururus chinensis, on lipopolysaccharide-induced interleukin-1β in RAW 264.7 cells

Park¹,

Bae²,

Chang-hyun³

et al. 2012

Korean J Anesthesiol

View full text Add to dashboard Cite

BackgroundElevated systemic levels of pro-inflammatory cytokines cause hypotension during septic shock and induce capillary leakage in acute lung injury. Manassantin B has anti-inflammatory and anti-plasmoidal properties. This study examined the effects of manassantin B on lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages.MethodsRAW 264.7 macrophage cells were incubated without or with (1, 3 and 10 µM) manassantin B and without or with (100 ng/ml) LPS. Manassantin B dissolved in phosphate buffered saline was added to the medium 1 h prior to the addition of LPS. The degree of activation of mitogen-activated protein kinase (MAPK) including extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Jun amino terminal kinases (JNK) and p38 MAPK, and the level of interleukin (IL)-1β were determined 30 min and 24 h after the addition of LPS respectively.ResultsManassantin B inhibited the production of IL-1β and attenuated the phosphorylations of ERK1/2 and p38 MAPK, but not that of JNK, in RAW 264.7 cells treated with LPS.ConclusionsManassantin B reduces LPS-induced IL-1β expression through effects on ERK1/2- and p38 MAPK-mediated pathways. Manassantin B has potential as a potent anti-inflammatory drug for use in pathological processes such as sepsis or acute lung injury.

show abstract

Total Synthesis and Stereochemical Confirmation of Manassantin A, B, and B₁

Abstract: Stereocontrolled total syntheses of manassantins A, B, and B1 and saucerneol are described for the first time based on a novel cycloetherification of end-differentiated benzylic alcohols as a common intermediate. [structure: see text].

Cited by 55 publications

References 27 publications

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

Anti-proliferative Neolignans from <i>Saururus chinensis</i> against Human Cancer Cell Lines

Effect of manassantin B, a lignan isolated fromSaururus chinensis, on lipopolysaccharide-induced interleukin-1β in RAW 264.7 cells

Contact Info

Product

Resources

About

Total Synthesis and Stereochemical Confirmation of Manassantin A, B, and B1

Abstract: Stereocontrolled total syntheses of manassantins A, B, and B1 and saucerneol are described for the first time based on a novel cycloetherification of end-differentiated benzylic alcohols as a common intermediate. [structure: see text].

Cited by 55 publications

References 27 publications

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

A Synthetic Manassantin A Derivative Inhibits Hypoxia-Inducible Factor 1 and Tumor Growth

Anti-proliferative Neolignans from <i>Saururus chinensis</i> against Human Cancer Cell Lines

Effect of manassantin B, a lignan isolated fromSaururus chinensis, on lipopolysaccharide-induced interleukin-1β in RAW 264.7 cells

Contact Info

Product

Resources

About

Total Synthesis and Stereochemical Confirmation of Manassantin A, B, and B₁