Synthesis, isolation and characterisation of β-sitosterol and β-sitosterol oxide derivatives

McCarthy, Florence O.; Chopra, Jay; Ford, Alan; Hogan, Sean A.; Kerry, Joe P.; O’Brien, Nora M.; Ryan, Eileen; Maguire, Anita R.

doi:10.1039/b505069c

Cited by 54 publications

(57 citation statements)

References 24 publications

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“…The implications of POPs in atherosclerosis, neurodegenerative processes and other chronic diseases are still unknown. However, they have been associated with cytotoxic and pro-apoptotic effects (Meyer et al, 1998;Adcox et al, 2001;McCarthy et al, 2005).…”

Section: Toxicity and Pathological Effects Of Oxysterolsmentioning

confidence: 99%

Oxysterols: A world to explore

Otaegui-Arrazola

Menéndez-Carreño

Ansorena

et al. 2010

Food and Chemical Toxicology

200

185

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Oxysterols (oxidized derivatives of cholesterol an phytosterols) can be generated in the human organism through different oxidation processes, some requiring enzymes.Furthermore, oxysterols are also present in food due to lipid oxidation reactions caused by heating treatments, contact with oxygen, exposure to sunlight, etc., and they could be absorbed from the diet, at different rates depending on their side chain lenght.In the organism, oxysterols can follow different routes: secreted into the intestinal lumen, esterified and distributed by lipoproteins to different tissues or degraded, maily in the liver. Cholesterol oxidation products (COPs) have shown citotoxicity, apoptotic and pro-inflammatory effects and they have also been linked with chronic diseases including atherosclerotic and neurodegenerative processess. In the case of phytosterols oxidation products (POPs), the evidences for toxic effects need more research. Nevertheless, current knowledge suggest their relation to cytotoxic and proapoptotic effects, although at higher concentrations than COPs.Recently, new beneficial biological activities of oxysterols are being under research. Whereas COPs are associated with cholesterol homeostasis mediated by different mechanisms, the implication of POPs is not clear yet.Available literature on sources of oxysterols in the organism, metabolism, toxicity and potential benefitial effects of these compounds are reviewed in this paper.2

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Section: Toxicity and Pathological Effects Of Oxysterolsmentioning

confidence: 99%

Oxysterols: A world to explore

Otaegui-Arrazola

Menéndez-Carreño

Ansorena

et al. 2010

Food and Chemical Toxicology

200

185

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“…Chemical structures of the identified compounds (l " Fig. 3) were determined by spectral analysis and compared to previously published data [10][11][12][13][14][15][16]. All compounds were tested in triplicate on the DV-NS5 RdRp at 10 µg/mL, followed by IC 50 determination of the DV-NS5 RdRp and full length DV-NS5 (constituted of both N-terminal RdRp and C-terminal methyltransferase).…”

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confidence: 99%

Biflavonoids ofDacrydium balansaewith Potent Inhibitory Activity on Dengue 2 NS5 Polymerase

et al. 2012

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In order to find new molecules for antiviral drug design, we screened 102 ethyl acetate extracts from New-Caledonian flora for antiviral activity against the dengue 2 virus RNA-dependant RNA polymerase (DV-NS5 RdRp). The leaf extract of Dacrydium balansae, which strongly inhibited the DV-NS5, was submitted to bioguided fractionation. Four biflavonoids ( 1- 4), three sterols ( 5- 7), and two stilbene derivatives ( 8- 9) were identified and evaluated for their antiviral potential on the DV-NS5 RdRp. Biflavonoids appeared to be potent inhibitors of DV-NS5 RdRp with IC (50)s between 0.26 and 3.12 µM. Inhibitory activity evaluations against the RNA polymerase from other Flaviviridae viruses allowed us to conclude that these compounds are specific inhibitors of the DV RNA polymerase. The strongest inhibitions were observed with hinokiflavone ( 4), but podocarpusflavone A ( 2) is the strongest noncytotoxic inhibitor of the DV-NS5 and it also displayed polymerase inhibitory activity in a DV replicon. A preliminary structure-activity relationship study (SARs) revealed the necessity of the biflavonoid skeleton, the influence of number and position of methoxylations, and the importance of a free rotation of the linkage between the two apigenin monomers of the biflavonoids. To the best of our knowledge, podocarpusflavone A ( 2) is the strongest noncytotoxic non-nucleotide molecule exhibiting a specific inhibitory activity against the RNA polymerase domain of DV-NS5 and thus is promising for chemotherapy development against dengue fever.

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“…While there has been a long standing high level of interest in the biological effects of cholesterol [16][17][18][19][20] and the phytosterols with recent studies on the biological activity of the oxides of phytosterols, [21][22][23][24][25][26] interest in lanosterol and its oxidation products has been a much more recent development. The isolation of lanostane type compounds from various natural sources and their biological evaluation has been documented.…”

Section: Introductionmentioning

confidence: 99%