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.
Synthesis of osthol-based botanical fungicides and their antifungal application in crop protection
Guo, Yuying,Chen, Jiabao,Ren, Dan,Du, Bo,Wu, Lei,Zhang, Yuanyuan,Wang, Zhouyu,Qian, Shan
, (2021/05/13)
Plant pathogenic fungi decrease the quality and productivity of plant production. The botanical fungicides have better biocompatibility and rapid biodegradation, little or no cross resistance, and the structural diversity, and thus are beneficial to deal with plant fungal diseases. Osthole has been widely used as the commercial botanical fungicide against powdery mildew in China. In this article, a series of osthole derivatives were synthesized, which respectively contain different substituents on the benzene ring, at the C8-position and pyrone ring. All the target compounds were evaluated in vitro for their antifungal activity against resistant phytopathogenic fungi. Colletotrichum fragariae, Strawberry Botrytis Cinerea, Kiwifruit Botrytis Cinerea, Kiwifruit brown Rots, which are common in fruit fungal diseases. The compound C4 was identified as the most promising candidate with the EC50 values at 38.7 μg/mL against Colletotrichum Fragariae, 14.5 μg/mL against Strawberry Botrytis Cinerea and 24.3 μg/mL against Kiwifruit Botrytis Cinerea, respectively, whereas the antifungal activity against resistant phytopathogenic fungi. of osthole is too low to be used (EC50 > 400 ppm). The results of mycelial relative conductivity determination, PI uptake and fluorescence spectroscopy indicated that the cell membrane of fungi is the key action site of C4. Besides, C4 has the potent inhibitory activity against both of plant and human pathogenic bacteria. Our studies showed that C4 was worthy for further attention as a promising botanical fungicide candidate in crop protection.
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).
Design, synthesis and biological evaluation of novel osthole-based derivatives as potential neuroprotective agents
Zhang, Li,Wu, Yuhang,Yang, Guixiang,Gan, Haixian,Sang, Dayong,Zhou, Jiye,Su, Lin,Wang, Rui,Ma, Lei
supporting information, (2020/11/03)
A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and Aβ42(Amyloid β-protein 42)-induced neurotoxicity were evaluated by MTT assays. Mechanism of the action of selected compounds were investigated by molecular docking. AlogP, logS and blood–brain barrier (BBB) permeability of all these compounds were simulated by admetSAR. Most of the compounds showed better antioxidative and anti-inflammatory activities compared with osthole, especially OST7 and OST17. The compound OST7 showed relative high activity in neuroprotection against H2O2 (45.7 ± 5.5%), oxygen glucose deprivation (64.6 ± 4.8%) and Aβ42 (61.4 ± 5.2%) at a low concentration of 10 μM. EC50 of selected compounds were measured in both H2O2 and OGD induced cytotoxicity models. Moreover, NO inhibiting ability of OST17(50.4 ± 7.1%) already surpassed the positive drug indomethacin. The structure activity relationship study indicated that introduction of piperazine group, tetrahydropyrrole group and aromatic amine group might be beneficial for enhancement of osthole neuroprotective properties. Molecular docking explained that the reason OST7 exhibited relatively stronger neuroprotection against Aβ because of the greater area of interactions between molecule and target protein. OST7 and OST17 both provided novel methods to investigate osthole as anti-AD drugs.
Synthesis of coumarin derivatives and their cytoprotective effects on t-BHP-induced oxidative damage in HepG2 cells
Ando, Tomomi,Nagumo, Mina,Ninomiya, Masayuki,Tanaka, Kaori,Linhardt, Robert J.,Koketsu, Mamoru
, p. 2422 - 2425 (2018/06/20)
Coumarins are ubiquitous in higher plants and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of coumarin derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in human hepatoma HepG2 cells. A series of coumarin derivatives were prepared and assessed for their cytoprotective effects. Among these, a caffeoyl acid-conjugated dihydropyranocoumarin derivative, caffeoyllomatin, efficiently protected against cell damage elicited by t-BHP. Our findings suggest that caffeoyllomatin appears to be a potent cytoprotective agent.
RT/PR dual-target HIV inhibitor, preparation method and applications thereof
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Paragraph 0057; 0090; 0092; 0093, (2018/09/11)
The invention discloses an RT/PR dual-target HIV inhibitor, a preparation method and applications thereof. According to the present invention, the RT/PR dual-target HIV inhibitor is prepared from a compound represented by a formula 1, or a pharmaceutically acceptable salt thereof, wherein the compound represented by the formula 1 has obvious inhibition activity on HIV reverse transcriptase and HIVprotease; and the toxicity study results show that the compound has good drug-forming property, such that the compound as the anti-acquired immunodeficiency syndrome drug has good application prospects. The formula I is defined in the specification.
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.
Accessing columbianetin-containing natural products via a domino on-water, in-water process
Beare, Kaitlin D.,McErlean, Christopher S.P.
, p. 1056 - 1058 (2013/04/10)
A domino on-water, in-water process has been developed for the rapid and efficient synthesis of (±)-columbianetin. This highlights the operational simplicity of on-water chemistry. The domino process forms the key step in the synthesis of the columbianetin-containing natural products (±)- columbianetin acetate, (±)-zosimin, (±)-libanorin and (±)-angelmarin.
Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor
Marumoto, Shinsuke,Miyazawa, Mitsuo
supporting information; experimental part, p. 784 - 788 (2012/03/22)
The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of β-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31), which has an IC50 value of 9.9 μM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5- methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC50 values 25.0 μM. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18, 31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by coumarins 24 was non-competitive inhibitors.
