Polyhydroxylated Steroids Research Articles

Synthesis and acetylcholinesterase inhibitory activity of polyhydroxylated sulfated steroids: Structure/activity studies

Disulfated and trisulfated steroids have been synthesized from cholesterol and their acetylcholinesterase inhibitory activity has been evaluated. In our studies we have found that the activity was not only dependent on the location of the sulfate groups but on their configurations. 2β,3α,6α-trihydroxy-5α-cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of 15.48μM comparable to that of 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (1). Both compounds were found to be less active than the reference compound eserine. The butyrylcholinesterase activity of 1 and 18 was one magnitude lower than that against acetylcholinesterase revealing a selective inhibitor profile.

Polyhydroxylated Steroids from the South China Sea Gorgonian Anthogorgia sp.

AbstractFour new polyhydroxylated steroids, namely anthogorgsteroids A–D (1–4), were isolated from the South China Sea gorgonian Anthogorgia sp. The structures of these compounds were elucidated by detailed spectroscopic analyses and comparison with reported data.

Theonellasterols and Conicasterols from Theonella swinhoei. Novel Marine Natural Ligands for Human Nuclear Receptors

Silica gel column chromatography, followed by HPLC purification on the apolar fraction of the methanol extract of marine sponge Theonella swinhoei, resulted in the isolation of a library of 10 polyhydroxylated steroids which we named theonellasterols B-H (1-7) and conicasterols B-D (8-10). The structures were determined on the basis of extensive spectroscopic data (MS, (1)H and (13)C NMR, COSY, HSQC, HMBC, and ROESY) analysis, and the putative binding mode to nuclear receptors (NRs) has been obtained through docking calculations. Pharmacological and structure-activity relationship analysis demonstrate that these natural polyhydroxylated steroids are potent ligands of human nuclear pregnane receptor (PXR) and modulator of farnesoid-X-receptor (FXR). In addition, the molecular characterization of theonellasterol G allowed the identification of the first FXR modulator and PXR ligand so far identified. Exposure of liver cells to this agent resulted in potent induction of PXR-regulated genes and modulation of FXR-regulated genes, highlighting its pharmacological potential in the treatment of liver disorders.

Anti-Inflammatory Polyoxygenated Steroids from the Soft Coral Sinularia sp.

Abstract Four new polyhydroxylated steroids (1–4) were isolated from a Formosan soft coral Sinularia sp. The structures of these metabolites were determined on the basis of spectroscopic (IR, MS, and 1D and 2D NMR) analyses. Among these metabolites, 3 and 4 are rarely found marine steroids with a C-9/C-10 double bond. Compounds 1 and 2 have shown significant inhibition of the accumulation of the pro-inflammatory COX-2 protein of LPS-stimulated RAW264.7 macrophage cells at 10 μM.

Structures of New Polar Steroids from the Far‐Eastern Starfish Ctenodiscus crispatus.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Two New Polyhydroxylated Steroids from the Hainan Soft CoralSinularia sp.

Two new polyhydroxylated steroids, (2β,3β,4α,5α,8β,11β)-4-methylergost-24(28)-ene-2,3,8,11-tetrol-(1) and (3β,5α,6β)-ergosta-22,24(28)-diene-3,5,6,19-tetrol (3), together with the six known related steroids 2 and 4–8, were isolated from the Hainan soft coral Sinularia sp. Their structures were elucidated on the basis of spectroscopic analysis and by comparison with previously reported data. The structure of the known compound 9 (hyrtiosterol) was revised as 2 by extensive analysis of the ROESY data and by the NOE difference experiment.

Dysideasterols A—E, Five New Uncommon Polyhydroxylated Steroids from the South China Sea Sponge Dysidea sp.

ChemInformVolume 36, Issue 27 Natural Products Dysideasterols A—E, Five New Uncommon Polyhydroxylated Steroids from the South China Sea Sponge Dysidea sp. Xiao-Chun Huang, Xiao-Chun Huang State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this authorYue-Wei Guo, Yue-Wei Guo State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this authorErnesto Mollo, Ernesto Mollo State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this authorGuido Cimino, Guido Cimino State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this author Xiao-Chun Huang, Xiao-Chun Huang State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this authorYue-Wei Guo, Yue-Wei Guo State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this authorErnesto Mollo, Ernesto Mollo State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this authorGuido Cimino, Guido Cimino State Key Lab. Drug Res., Shanghai Inst. Mater. Med., Chin. Acad. Sci., Shanghai 200031, Peop. Rep. ChinaSearch for more papers by this author First published: 16 June 2005 https://doi.org/10.1002/chin.200527183Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume36, Issue27July 5, 2005 RelatedInformation

Structures of new polar steroids from the Far-Eastern starfish Ctenodiscus crispatus

A fraction of sulfated polyhydroxylated steroids from the Far-Eastern starfish Ctenodiscus crispatus was investigated. The main component of this fraction was identified as (22E,24R,25R)-24-methyl-5α -cholest-22-en-3β,5,6β,15α,25,26-hexol 26-O-sulfate. For the compound stereoisomeric with respect to the side chain, the (24R,25S) or (24S,25R) relative configurations were assigned to the C(24) and C(25) chiral centers. The structures of two other compounds isolated from the fraction were identified as (22E, 24ξ)-26,27-bisnor-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25-pentol 25-O-sulfate and (22E, 24ξ,25ξ)-24-methyl-5α-cholest-22-en-3β,5,6β,8,15α,25,26-heptol 26-O-sulfate.

Dysideasterols A-E, Five New Uncommon Polyhydroxylated Steroids from the South China Sea SpongeDysidea sp.

Five new uncommon polyhydroxylated steroids, dysideasterols A–E (1–5), were isolated from the South China Sea sponge Dysidea sp. Their structures were established by detailed analysis of spectral data and verified via single-crystal X-ray-diffraction analysis of compound 1. The absolute configuration of 1 was determined by the modified Mosher method.

Seasonal variations in the levels of polyhydroxysteroids and related glycosides in the digestive tissues of the starfish Patiria ( Asterina) pectinifera

Seasonal variations in the levels of polar steroids including polyhydroxylated steroids and related glycosides in digestive organs of the starfish Patiria (= Asterina) pectinifera have been studied. The concentration of polar steroids is related to the annual reproductive cycle of the starfish and periods of active feeding. Two peaks in concentrations of polar steroids in pyloric caeca and stomach were found, the first in winter during reorganization and the second in summer during intensive gametogenesis before spawning. Probable biological functions of polyhydroxysteroids and related glycosides are discussed. The data support the hypothesis these compounds are involved in digestion in the starfish.

Comparative study on polyhydroxylated steroids from echinoderms

Eight polar steroids were identified from nine species of ophiuroids. Seven polyhydroxylated steroids were isolated from the sea lily Heliometra glacialis maxima. The relationship between compositions of polar steroid fractions in ophiuroids and systematic positions of the animals are discussed.

A novel sulphated steroid with a 7-membered 5-oxalactone B-ring from an Antarctic starfish of the family Asteriidae

Three novel sulphated polyhydroxylated steroids, named asterasterols A-C (1-3), have been isolated from an Antarctic starfish of the family Asteriidae and their structures elucidated by spectroscopic studies. Steroid 1 has the seven-membered 5-oxalactone B-ring; 2 and 3 are the corresponding 6-oxo steroids. © 1997 Published by Elsevier Science Ltd. In connection with our systematic investigation of steroid constituents from echinoderms, we examined some Antarctic starfish species, t'2 These studies have led to the isolation of a series of sulfated polyhydroxysteroids and steroidal glycosides structurally very close, some identical, with those found in species collected in warm environments. 3 During the investigation of the polar extracts of an Antarctic starfish of the family Asteriidae, which is the subject of this report, we have isolated a structurally novel steroid exhibiting 7-membered 5- oxalactone B-ring, along with the corresponding 6-oxo steroids. The starfish, Asteriidae family, was collected in Tethis Bay during the Italian-Antarctic expedition in January 1990 at a depth of 50-100 mt. The starfish (500 g fresh) was extracted with water and then with acetone; from the aqueous extract the sulphated steroids and steroidal glycosides were recovered by passing it through a column of Amberlite, washing out salts with distilled water, and eluting the absorbed material with methanol. The acetone extracts were solvent partitioned between water and n-butanol. The combined methanol eluate and n-butanol soluble material, were separated by sequential application of gel permeation on Sephadex LH- 60, DCCC and HPLC, to give the sulphated steroids 1-3, in small amounts, ranging from 7.2 mg of 1 (major) to 3.4 mg of 3 (minor).

ChemInform Abstract: Regioselective Esterification of Polyhydroxylated Steroids by Candida antarctica Lipase B.

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Two polyhydroxylated steroids from the Chinese soft coral Litophyton arboreum

Two polyhydroxylated steroids have been isolated from the South China Sea soft coral Litophyton arboreum, and their structures were established as 24-methylcholesta-5,24(28)-diene-3β, 7β,19-triol and (24E)-24-ethyl-5α-cholesta-8,24(28)-diene-3β,12β,19-triol from spectral evidence.

Structures of novel bufadienolides in the eggs of a toad, Bufo marinus.

In this paper, we report chemical structures of five compounds including four novel polyhydroxylated cardiac steroids in the eggs of a toad, Bufo marinus. These cardiac steroids were purified by high-performance liquid chromatography, and their structures were determined to be 11 alpha,19-dihydroxy-telocinobufagin (I), 11 alpha-hydroxytelocinobufagin (II), 11 alpha,19-dihydroxymarinobufagin (III), 11 alpha-hydroxymarinobufagin (IV) and 19-hydroxytelocinobufagin (V) on the basis of spectral data of nuclear magnetic resonance and mass spectroscopy. All the five compounds showed biological activity, as tested by inhibition of Na+,K(+)-ATPase activity and of [3H]ouabain binding to the receptor on Na+,K(+)-ATPase. This is the first finding of bufadienolides as cardiac steroids in animal eggs.

ChemInform Abstract: Phosphated and Sulfated Marine Polyhydroxylated Steroids from the Starfish Tremaster novaecaledoniae.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Two polyhydroxylated steroids from the Chinese soft coral Sinularia microclavata

Two polyhydroxylated steroids have been isolated from the South China Sea soft coral Sinularia microclavata, and their structures were established as 24-methylenecholestane-1α,3β,5α,6β-tetrol and 1α,3β,5α-trihydroxy-24-methylenecholestan-6-one from spectral evidence and from comparison with two reference compounds, numersterol A and 24-methylenecholestane-1α,3β,5α,6β,25-pentol, which were isolated from the soft corals, Simularia numerosa and Sarcophyton glaucum, respectively.

Stereoselective synthesis of (24S)- and (24R)-24-(hydroxymethyl)cholesta-5,22(E)-dien-3.beta.-ol: model compounds for stereochemical assignments of polyhydroxylated marine steroids

Synthese des stereoisomeres 24R et 24S, methoxy-6β cyclo-3α,5 ergostane-5α ol-28 et 22E,24R et 22E,24S-ergostadiene-5,22diol-3β,28 a partir de 22R et 22S methoxy-6β cyclo-3α,5 pregnanecarbaldehyde-20 et de t-butyldimethylsilyl propyne-2yl ether

Synthesis of 24-methyl-26-hydroxysteroid side-chains: models for stereochemical assignments in polyhydroxylated marine steroids

Stereoisomers of Δ22E and saturated 24-methyl-26-hydroxy steroids have been synthesized via a Claisen rearrangement as model compounds of established absolute configuration for stereochemical assignments at C-24 and C-25 of marine 24-methyl-26-hydroxy steroids. Analysis of NMR spectral data of synthetic compounds and of their MTPA esters proved the suitability of NMR spectroscopy for the assignment of configurations at C-24 and C-25 of unknown 24-methyl-26-hydroxy steroids. The absolute configurations at C-24 and C-25 of two naturally occurring marine steroids from a starfish and an ophiuroid have been established.

Activities of novel polyhydroxylated cardiotonic steroids purified from nuchal glands of the snake, Rhabdophis tigrinus.

Seven novel polyhydroxylated steroids were isolated from the nucho-dorsal glands of the snake, Rhabdophis tigrinus. Biological activities of these steroids in inhibiting (Na+ + K+)ATPase and in producing positive inotropic action were examined in comparison with those of ouabain and gamabufotalin. Gamabufotalin was approximately 10 times more potent than ouabain in inhibiting (Na+ + K+)ATPase. Two compounds, compounds III and XIII, of the seven, produced nearly equipotent enzyme inhibitory activity to ouabain. The activity of the remaining five was relatively low among the compounds tested. All compounds exhibited more or less positive inotropic action in the papillary muscle preparations. The ranking order of the potency was: gamabufotalin greater than ouabain and compound IV greater than compound III and XIII greater than compound I, II, XII and XIV.