484-14-0Relevant articles and documents
Selective Inhibitory Effect of Osthenol on Human Cytochrome 2C8
Cho, Pil Joung,Nam, WoongShik,Lee, Doohyun,Lee, Taeho,Lee, Sangkyu
, p. 801 - 805 (2018)
Osthenol is a furanocoumarin with anti-tumor, anti-inflammatory, and anti-viral activity. It is present in various citrus juices and fruits; however, its inhibitory effects on cytochrome P450 (CYP) enzyme activity, in the context of herb–drug interaction (HDI) prediction, have not been previously studied. In this study, osthenol was chemically synthesized in order to identify potential HDIs. Its inhibitory effect on eight CYP isoforms and the underlying mechanism of inhibition were investigated by using cocktail assays and liquid chromatography-tandem mass spectrometry in pooled human liver microsomes. The inhibitory effect of osthenol on CYP2C8-catalyzed paclitaxel hydroxylation was selective and dose-dependent, but not time-dependent. The IC50 value was 2.8 μM. Additionally, osthenol displayed mixed mode inhibition with a relatively low Ki value of 0.96 μM, which is indicative of the potential for HDIs with co-administered CYP2C8 substrates. To the best of our knowledge, this is the first report of selective inhibition of CYP2C8 by osthenol.
Design and synthesis of Osthole-based compounds as potential Nrf2 agonists
Cui, Jiayan,Huang, Jin,Huang, Weiwei,Huang, Yi,Ma, Lei,Wu, Yuhang,Zhu, Fuli
supporting information, (2022/02/21)
A total of 23 compounds based on Osthole skeleton were designed and synthesized. Their agonistic activity for Nrf2 were evaluated by Dual-luciferase Reporter Gene Assay. Most of the compounds showed better activities compared with Osthole, especially O15 and O21. And the median effective concerntration (EC50) values was calculated accordingly, both of which showed remarkable activity for Nrf2. The structure activity relationship study indicated that introduction of the structure of stilbene might be beneficial for enhancement of agonistic properties of Osthole, and the position of the substituent may have a greater effect on the activity than the electron-donating/withdrawing ability of the substituent. Mechanism of the action of selected compound O15 was investigated by molecular docking, cellular thermal shift assay and ubiquitination assay, which suggested the reason why O15 exhibited relatively stronger agonistic activity for Nrf2. Compound O15 and O21 both provided novel methods to investigate Osthole-based compounds as Nrf2 agonists.
PROCESSES FOR THE PREPARATION OF ORTHO-ALLYLATED HYDROXY ARYL COMPOUNDS
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Paragraph 00348; 00377, (2021/12/08)
The present application describes process for preparing an ortho-allylated hydroxy aryl compounds such as compounds of Formula (I) by reacting an allylic alcohol with a hydroxy aryl compound in the presence of aluminum compound selected from alumina and aluminum alkoxides and in a non-protic solvent wherein at least one carbon atom ortho to the hydroxy group in the hydroxy aryl compound is unsubstituted. The present application also includes compounds of Formula (I).
Prenylcoumarins in One or Two Steps by a Microwave-Promoted Tandem Claisen Rearrangement/Wittig Olefination/Cyclization Sequence
Schultze, Christiane,Schmidt, Bernd
, p. 5210 - 5224 (2018/05/17)
The one-pot synthesis of 8-prenylcoumarins from 1,1-dimethylallylated salicylaldehydes and the stabilized ylide [(ethoxycarbonyl)methylene]triphenylphosphorane under microwave conditions was found to have a limited scope. The sequence suffers from a difficult and sometimes low-yielding synthesis of the precursors and from a competing deprenylation upon microwave irradiation. This side reaction occurs in particular with electron rich arenes with two or more alkoxy groups at adjacent positions, a prominent substitution pattern in naturally occurring 8-prenylcoumarins. Both limitations of this one-step sequence were overcome by a two-step synthesis consisting of a microwave-promoted tandem allyl ether Claisen rearrangement/Wittig olefination and a subsequent olefin cross metathesis with 2-methyl-2-butene. The cross metathesis step proceeds with a high selectivity and yields exclusively the desired prenyl, rather than the alternative crotyl substituent. Several naturally occurring 8-prenylcoumarins that were previously inaccessible have been synthesized in good overall yields along this route.