- Pyranocoumarin derivative as well as preparation method and application thereof
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The invention belongs to the technical field of medicine, and relates to a pyranocoumarin derivative, a preparation method and uses thereof. The pyranocoumarin derivative has a structural general formula represented by a formula I, wherein R is H, halogen, OH, NH2, COOH, C1-C6 alkyl, C1C6 alkoxy, C1-C6 alkylamino, and 5-10-membered heterocyclic group, and n is 06. The pyranocoumarin derivative isapplied to preparation of a medicine for preventing and treating prostatic cancer. According to the application disclosed by the invention, the inhibition effect of the peucedanum praeruptorum alcoholesterification derivative substituted at the 3' position of the pyranoid ring in the pyranoid coumarin on human prostate cancer cells is proved by evaluating the in-vitro inhibition activity of the peucedanum praeruptorum alcohol esterification derivative substituted at the 3' position of the pyranoid ring in the pyranoid coumarin on human prostate cancer cells; the compound can be used as a potential drug for preventing and treating prostate cancer for deep development, and has important practical value and application prospect in the field of preparation of antitumor drugs.
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Paragraph 0023-0025
(2021/03/13)
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- Discovery of tricyclic pyranochromenone as novel bruton’s tyrosine kinase inhibitors with in vivo antirheumatic activity
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Bruton’s tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK. We screened an in-house library of natural products and their analogs via a biochemical assay to identify a novel scaffold for targeting BTK. A pyranochromenone scaffold, derived from a natural active component decursin, was found to be effective at targeting BTK and was selected for further optimization. A series of pyranochromenone analogs was synthesized through the modification of pyranochromenone at the C7 position. Pyranochromenone compounds with an electrophilic warhead exhibited promising BTK inhibitory activity, with IC50 values in the range of 0.5–0.9 μM. A docking study of the representative compound 8 provided a reasonable explanation for compound activity. Compound 8 demonstrated good selectivity over other associated kinases and decreased the production of proinflammatory cytokines in THP cells. Moreover, compound 8 presented significant in vivo efficacy in a murine model of collagen-induced arthritis.
- Cho, Hyewon,Jeon, Hui-Jeon,Jeon, Raok,Kwon, Hye Ah,Lee, Eun,Ryu, Jae-Ha,Seul, Lee,Yu, Ji Hoon
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- A simple and efficient approach for the preparation of dihydroxanthyletin, xanthyletin, decursinol and marmesin
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A simple and efficient approach has been developed for the preparation of coumarin natural products such as dihydroxanthyletin, xanthyletin, decursinol and marmesin starting from commercially available 2,4-dihydroxybenzaldehyde with very good yields. Wittig homologation and Claisen rearrangement are the protocols used to achieve these molecules.
- Kommera, Rajkumar,Bhimapaka, China Raju
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p. 3204 - 3211
(2020/08/05)
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- Synthesis of coumarin derivatives and their cytoprotective effects on t-BHP-induced oxidative damage in HepG2 cells
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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.
- Ando, Tomomi,Nagumo, Mina,Ninomiya, Masayuki,Tanaka, Kaori,Linhardt, Robert J.,Koketsu, Mamoru
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p. 2422 - 2425
(2018/06/20)
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- Synthesis and in vitro assay of new triazole linked decursinol derivatives showing inhibitory activity against cholinesterase for Alzheimer's disease therapeutics
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With the goal of developing Alzheimer's disease therapeutics, we have designed and synthesized new triazole linked decursinol derivatives having potency inhibitory activities against cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (B
- Park, Jung-Youl,Shin, Sujeong,Park, Kyoung Chan,Jeong, Eunju,Park, Jeong Ho
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p. 125 - 130
(2016/04/19)
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- A synthetic decursin analog with increased in vivo stability suppresses androgen receptor signaling in vitro and in vivo
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Summary: Targeting androgen receptor (AR) signaling with agents distinct from current antagonist drugs remains a rational approach to the prevention and treatment of prostate cancer (PCa). Our previous studies have shown that decursin and isomer decursinol angelate (DA), isolated from the Korean medicinal herb Angelica gigas Nakai, interrupt AR signaling and possess anti-PCa activities in vitro. In the LNCaP PCa cell model, these pyranoccoumarin compounds exhibit properties distinct from currently used antagonists (e.g., Casodex). However, both are rapidly de-esterified to decursinol, a partial AR agonist. We report here that a synthetic decursin analog, decursinol phenylthiocarbamate (DPTC), has greater in vivo stability than the parent compounds. DPTC-decursinol conversion was undetectable in mice. Furthermore, in LNCaP cells, DPTC decreased prostate specific antigen (PSA) expression, down-regulated AR abundance and mRNA and inhibited AR nuclear translocation. The effect of DPTC on AR and PSA mRNA and protein abundance was also observed in VCaP cells expressing wild type AR. DPTC inhibited growth of both PCa cell lines through G1 cell cycle arrest and apoptosis, as did decursin and DA. Furthermore, i.p. administration of DPTC for 3 weeks suppressed the expression of AR target genes probasin and Nkx3.1 in mouse prostate glands. Overall, our data suggest that DPTC represents a prototype lead compound for development of in vivo stable and active novel decursin analogs for the prevention or therapy of PCa.
- Zhang, Yong,Shaik, Ahmad Ali,Xing, Chengguo,Chai, Yubo,Li, Li,Zhang, Jinhui,Zhang, Wei,Kim, Sung-Hoon,Lü, Junxuan,Jiang, Cheng
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p. 1820 - 1829
(2013/01/15)
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- Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor
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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.
- Marumoto, Shinsuke,Miyazawa, Mitsuo
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supporting information; experimental part
p. 784 - 788
(2012/03/22)
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- Decursin and decursinol angelate selectively inhibit NADH-fumarate reductase of Ascaris suum
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NADH-fumarate reductase (NFRD) is a key enzyme in many anaerobic helminths. Decursin and decursinol angelate have been isolated from the roots of Angelica gigas Nakai (Apiaceae) as NFRD inhibitors. They inhibited Ascaris suum NFRD with IC50 values of 1.1 and 2.7 μM, respectively. Their target is the electron transport enzyme complex I. Since the inhibitory activities of decursin against bovine heart complexes are weak, it is a selective inhibitor of the nematode complex I. In contrast, decursinol angelate moderately inhibits bovine heart complexes II and III. Decursinol inhibits A. suum NFRD to a similar extent, but its target is complex II. It also inhibits bovine heart complexes II and III. Georg Thieme Verlag KG Stuttgart.
- Shiomi, Kazuro,Hatano, Hiroko,Morimoto, Hiromi,Ui, Hideaki,Sakamoto, Kimitoshi,Kita, Kiyoshi,Tomoda, Hiroshi,Eun, Woo Lee,Tae, Ryeon Heo,Kawagishi, Hirokazu,Omura, Satoshi
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p. 1478 - 1481
(2008/09/20)
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- An efficient synthesis of (+)-decursinol from umbelliferone
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An efficient, practical and enantioselective total synthesis of (+)-decursinol, which has diverse range of biological properties including anti-cancer, anti-Helicobacter pylori, and strong antinociceptive activities, has been achieved in five steps with 41.4% overall yield from umbelliferone. The improved ring construction from coumarin to linear pyranocoumarin has been obtained through quinonemethide intermediate by using phenylboronic acid with propionic acid.
- Lee, Jung Ho,Bang, Hyun Bae,Han, Su Young,Jun, Jong-Gab
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p. 2889 - 2892
(2008/02/03)
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- Microbial metabolism. Part 8. The pyranocoumarin, decursin
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Microbial transformation of the cancer chemopreventive agent, decursin (1) with Sepedonium chrysospermem (ATCC 13378) yielded two metabolites, (+)-decursinol (2) and (-)-cis-decursidinol (3). The structures were established by spectroscopic data.
- Herath, Wimal,Reddy, Niranjan,Khan, Ikhlas Ahmad
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p. 1512 - 1513
(2008/03/12)
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- Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enone
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The enantioselective total syntheses of (+)-decursin (1) and related natural dihydropyranocoumarins (-)-prantschimgin (3), (+)-decursinol (4), and (+)-marmesin (5) were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. Catalytic asymmetric epoxidation of the enone was effectively promoted by the novel multifunctional asymmetric catalyst generated from La(O-i-Pr)3, BINOL, and Ph3As=O in a 1:1:1 ratio to afford epoxide in 94% yield and 96% ee, which was recrystallized to give optically pure epoxide. After conversion to the common key intermediate (-)-peucedanol (7), all natural dihydropyranocoumarins were synthesized through palladium-catalyzed intramolecular C-O coupling reactions. A possible reaction mechanism of the catalytic asymmetric epoxidation of enones is also described based on X-ray analysis, laser desorption/ionization time-of-flight mass spectrometry, kinetic studies, and asymmetric amplification studies.
- Nemoto, Tetsuhiro,Ohshima, Takashi,Shibasaki, Masakatsu
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p. 6889 - 6897
(2007/10/03)
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- PYRANOCOUMARIN DERIVATIVES
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The present invention relates to compounds of the following formula (I) or pharmaceutically acceptable salts thereof. The present invention also relates to use for a cognitive-enhancing agent of compounds of the following formula (I) or pharmaceutically a
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Page/Page column 8-9
(2008/06/13)
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- Enantioselective syntheses of decursinol angelate and decursin
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The practical enantioselective syntheses of decursinol angelate and decursin were achieved in eight steps from resorcinol. The stereochemistry was addressed using the catalytic asymmetric epoxidation of 7-acetoxy-2,2-dimethylchromene by chiral (salen)Mn complexes as the key step.
- Lim, Jongdoo,Kim, Ik-Hwan,Kim, Hyeon Ho,Ahn, Kyung-Seop,Han, Hogyu
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p. 4001 - 4003
(2007/10/03)
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- Enantioselective syntheses of (+)-decursinol and (+)-trans-decursidinol
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Selective and practical asymmetric syntheses of (+)-decursinol (1) and (+)-trans-decursidinol (2) have been achieved using naturally occurring umbelliferone, demethylsuberosin, and xanthyletin as the synthetic intermediates. The absolute stereochemistry was established in the late stage of synthesis by employing Jacobsen's enantioselective epoxidation conditions.
- Kim, Sanghee,Ko, Hyojin,Son, Soonjoo,Shin, Kye Jung,Kim, Dong Jin
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p. 7641 - 7643
(2007/10/03)
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- Enantioselective total syntheses of novel PKC activator (+)-decursin and its derivatives using catalytic asymmetric epoxidation of an enone
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The catalytic asymmetric total syntheses of (+)-decursin and three related natural products, (+)-decursinol, (-)-prantschimgin and (+)-marmesin, were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. The catalytic asymmetric epoxidation of enone was found to be promoted effectively by novel multifunctional asymmetric catalyst generated from La(O-i-Pr)3, BINOL and O=AsPh3 in a 1:1:1 ratio to afford epoxide in 94% yield and 96% ee, which was recrystallized to give the optically pure epoxide. (C) 2000 Elsevier Science Ltd.
- Nemoto,Ohshima,Shibasaki
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p. 9569 - 9574
(2007/10/03)
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- Anti-Helicobacter pylori activity of herbal medicines
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The extracts of Coptidis japonica (rhizoma), Eugenia caryophyllata (flower), Rheum palmatum (rhizoma), Magnolia officinalis (cortex) and Rhus javanica (galla rhois) potently inhibited the growth of Helicobacter pylori (HP). However, these herbal extracts showed no inhibitory effect on HP urease except Galla rhois. Among the components separated from active herbal extracts by silica gel column chromatography, the inhibitory effects of decursinol angelate and decursin on the growth of HP were the most potent, followed by magnolol, berberinc, cinnamic acid, decursinol and gallic acid. Minimum inhibitory concentrations (MICs) of decursin and decursinol angelate were 6-20 μg/ml.
- Bae, Eun-Ah,Han, Myung Joo,Kim, Nam-Jae,Kim, Dong-Hyun
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p. 990 - 992
(2007/10/03)
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