- Anti‐melanogenic properties of velutin and its analogs?
-
Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti‐inflammatory, anti‐allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti‐melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2‐diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural‐derived functional materials to regulate melanin synthesis.
- Choe, Jung-Won,Heo, Hee-Young,Jung, Se-Hui,Kim, Jaehyun,Lee, Kooyeon
-
-
- New homoisoflavonoid analogues protect cells by regulating autophagy
-
As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.
- Gan, Li-She,Zeng, Lin-Wei,Li, Xiang-Rong,Zhou, Chang-Xin,Li, Jie
-
supporting information
p. 1441 - 1445
(2017/03/08)
-
- NOVEL ANALOGUES OF EPICATECHIN AND RELATED POLYPHENOLS
-
The present invention provides novel analogues of epicatechin and related polyphenols, their variously functionalized derivatives, process for preparation of the same, composition comprising these compounds and their method of use.
- -
-
Paragraph 0189
(2016/03/05)
-
- Anti-proliferative effect of chalcone derivatives through inactivation of NF-κB in human cancer cells
-
To investigate the anti-proliferative effect of NF-κB inhibitor, a series of analogs of (E)-1-(2-hydroxy-6-(isopentyloxy)phenyl)-3-(4- hydroxyphenyl)prop-2-en-1-one (5a) were prepared and evaluated for their NF-κB inhibition and anti-proliferative activity against various human cancer cell lines. Compounds (E)-1-(2-(3,3-dimethylbutoxy)-6-hydroxyphenyl)-3- (4-hydroxyphenyl)prop-2-en-1-one (5e) and (E)-4-(3-(2-(3,3-dimethylbutoxy)-6- hydroxyphenyl)-3-oxoprop-1-enyl)benzenesulfonamide (5p) showed good NF-κB inhibition as well as potent anti-proliferative activity. SAR studies showed that all the compounds with potent or moderate NF-κB inhibition displayed good anti-proliferative activity. All the analogs (5b-r) maintained a good correlation between their NF-κB inhibition and anti-proliferative activity though the extent is not directly proportional to each other.
- Venkateswararao, Eeda,Sharma, Vinay K.,Yun, Jieun,Kim, Youngsoo,Jung, Sang-Hun
-
p. 3386 - 3392
(2014/06/23)
-
- Development of flavonoid-based inverse agonists of the key signaling receptor US28 of human cytomegalovirus
-
A series of 31 chalcone- and flavonoid-based derivatives were synthesized in good overall yields and screened for their inverse agonist activity on the US28 receptor of human cytomegalovirus (HCMV). With one exception (e.g., 2-(5-bromo-2-methoxyphenyl)-3-hydroxy-4H-chromen-4-one), halogen-substituted flavonoids were typically more potent inverse agonists than their related hydro derivatives. While toxicity could be used to partially explain the inverse agonist activity of some members of the series, 5-(benzyloxy)-2-(5-bromo-2- methoxyphenyl)-4H-chromen-4-one (11b) acted on the US28 receptor as a nontoxic, inverse agonist. The full inverse agonism (efficacy, -89%) and potency (EC 50 = 3.5 μM) observed with flavonoid 11b is especially important as it provides both a new tool to study US28 signaling and a potential platform for the future development of HCMV-targeting drugs.
- Kralj, Ana,Nguyen, Mai-Thao,Tschammer, Nuska,Ocampo, Nicolette,Gesiotto, Quinto,Heinrich, Markus R.,Phanstiel, Otto
-
p. 5019 - 5032
(2013/07/26)
-
- An efficient procedure for the preparation of natural products bearing the 2-(2-phenylethyl)chromone skeleton
-
Several 2-(2-phenylethyl)chromones have been shown to possess neuroprotective activity. However, limited synthetic methods have been disclosed to construct the 2-(2-phenylethyl)chromone skeleton. Herein, we report a straightforward 3-step preparation of f
- Williams, Dwight A.,Smith, Cameron,Zhang, Yan
-
p. 4292 - 4295
(2013/07/26)
-
- A one-pot synthesis of aurones from substituted acetophenones and benzaldehydes: A concise synthesis of aureusidin
-
A one-pot synthesis of aurones from substituted acetophenone and benzaldehyde has been developed on the basis of an improved Algar-Flynn-Oyamada reaction. By using this method, several aurones were prepared in three steps from commercial starting materials. The usefulness of this one-pot strategy was confirmed by a synthesis of aureusidin, an inhibitor of iodothyronine deiodinase, in 41% overall yield. In comparison with a two-step synthesis of this product from the same substrates, the one-pot strategy was more effective, giving a higher yield and requiring fewer and simpler operations. Georg Thieme Verlag Stuttgart New York.
- Zhao, Xiaolong,Liu, Jie,Xie, Zhixiang,Li, Ying
-
experimental part
p. 2217 - 2224
(2012/09/22)
-
- Substituted chromones as highly potent nontoxic inhibitors, specific for the breast cancer resistance protein
-
A series of 13 disubstituted chromones was synthesized. Two types of substituents, on each side of the scaffold, contributed to both the potency of ABCG2 inhibition and the cytotoxicity. The best compound, 5-(4-bromobenzyloxy)- 2-(2-(5-methoxyindolyl)ethy
- Valdameri, Glaucio,Genoux-Bastide, Estelle,Peres, Basile,Gauthier, Charlotte,Guitton, Jér?me,Terreux, Rapha?l,Winnischofer, Sheila M. B.,Rocha, Maria E. M.,Boumendjel, Ahcène,Di Pietro, Attilio
-
supporting information; experimental part
p. 966 - 970
(2012/03/10)
-
- A SAR study on a series of synthetic lipophilic chalcones as Inhibitor of transcription factor NF-κB
-
To define the structural features responsible for the activity of 2,4-dihydroxy-6-isopentyloxychalcone, a newly established inhibitor of LPS induced NF-κB activation (IC50 = 10 μM), a series of its analogues was prepared and studied for their i
- Venkateswararao, Eeda,Sharma, Vinay K.,Lee, Ki-Cheul,Sharma, Niti,Park, Sun-Hong,Kim, Youngsoo,Jung, Sang-Hun
-
experimental part
p. 379 - 386
(2012/10/08)
-
- Towards the first inhibitors of trihydroxynaphthalene reductase from Curvularia lunata: Synthesis of artificial substrate, homology modelling and initial screening
-
Trihydroxynaphthalene reductase (3HNR) is an essential enzyme in the biosynthesis of fungal melanin and it represents an emerging target for the development of new fungicides and antimicotics. To promote the discovery of new inhibitors, an improved chemic
- Brunskole, Mojca,Stefane, Bogdan,Zorko, Karmen,Anderluh, Marko,Stojan, Jure,Lanisnik Rizner, Tea,Gobec, Stanislav
-
p. 5881 - 5889
(2008/12/20)
-
- Structural basis for the activity of the RSK-specific inhibitor, SL0101
-
Inappropriate activity of p90 ribosomal S6 kinase (RSK) has been implicated in various human cancers as well as other pathologies. We previously reported the isolation, characterization, and synthesis of the natural product kaempferol 3-O-(3″,4″-di-O-acetyl-α-l-rhamnopyranoside), termed SL0101 [Smith, J. A.; Poteet-Smith, C. E.; Xu, Y.; Errington, T. M.; Hecht, S. M.; Lannigan, D. A. Cancer Res., 2005, 65, 1027-1034: Xu, Y.-M; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Bioorg. Med. Chem., 2006, 14, 3974-3977: Maloney, D. J.; Hecht, S. M. Org. Lett., 2005, 7, 1097-1099]. SL0101 is a potent and specific inhibitor of RSK; therefore, we performed an analysis of the structural basis for the inhibitory activity of this lead compound. In in vitro kinase assays we found that acylation of the rhamnose moiety and the 4′, 5, and 7-hydroxyl groups are responsible for maintaining a high affinity interaction of RSK with SL0101. It is likely that the hydroxyl groups facilitate RSK binding through their ability to form hydrogen bonds. To determine whether the SL0101 derivatives were specific for inhibition of RSK we analyzed their ability to preferentially inhibit the growth of the human breast cancer line, MCF-7, compared to the normal human breast line, MCF-10A. We have previously validated this differential growth assay as a convenient readout for analyzing the specificity of RSK inhibitors [Smith, J. A.; Maloney, D. J.; Clark, D. E.; Xu, Y.-M.; Hecht, S. M.; Lannigan, D. A. Bioorg. Med. Chem., 2006, 14, 6034-6042]. We found that acylation of the rhamnose moiety was essential for maintaining the selectivity for RSK inhibition in intact cells. Further, the efficacy of SL0101 in intact cells is limited by cellular uptake as well as possible hydrolysis of the acetyl groups on the rhamnose moiety by ubiquitous intracellular esterases. These studies should facilitate the development of a RSK inhibitor, based on the SL0101 pharmacophore, as an anti-cancer chemotherapeutic agent.
- Smith, Jeffrey A.,Maloney, David J.,Hecht, Sidney M.,Lannigan, Deborah A.
-
p. 5018 - 5034
(2008/03/12)
-
- FUSED HETEROCYCLIC DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND MEDICINAL USE THEREOF
-
The present invention provides fused heterocyclic derivatives represented by the general formula: wherein R1 represents H, halogen, OH, etc.; R2 represents H, halogen or an alkyl group; R3 and R4 represent H, OH, halogen, etc.; Q represents alkylene, etc.; ring A represents aryl or heteroaryl; and G represents or ???or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.
- -
-
Page/Page column 38
(2008/06/13)
-
- Synthesis and in vitro inhibitory activity on human platelet aggregation of novel properly substituted 4-(1-piperazinyl)coumarins
-
Pursuing our chemical and biological studies in this field, we described the multistep preparation of the new 5-, 6-, or 7-alkoxy and 7-alkoxy-8-methyl substituted 4-(1-piperazinyl)coumarins 5d-v, as well as the in vitro evaluation of their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen or the Ca2+ ionophore A23187. Compounds 5h-j,p,r-u showed notably high activity towards all the platelet aggregation inducers used, and the most active one, 8-methyl-4-(1-piperazinyl)- 7-(3-pyridylmethoxy)coumarin (5t), proved to be a potent in vitro antiplatelet agent.
- Di Braccio, Mario,Grossi, Giancarlo,Roma, Giorgio,Signorello, Maria Grazia,Leoncini, Giuliana
-
p. 397 - 409
(2007/10/03)
-
- Synthesis and structure-activity relationships of novel IKK-β inhibitors. Part 3: Orally active anti-inflammatory agents
-
A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as IκB kinase β (IKK-β) inhibitors. Modification of a novel IKK-β inhibitor 1 (IKK-β IC 50=1500nM, Cell IC50=8000nM) at the 4-p
- Murata, Toshiki,Shimada, Mitsuyuki,Sakakibara, Sachiko,Yoshino, Takashi,Masuda, Tsutomu,Shintani, Takuya,Sato, Hiroki,Koriyama, Yuji,Fukushima, Keiko,Nunami, Noriko,Yamauchi, Megumi,Fuchikami, Kinji,Komura, Hiroshi,Watanabe, Akihiko,Ziegelbauer, Karl B.,Bacon, Kevin B.,Lowinger, Timothy B.
-
p. 4019 - 4022
(2007/10/03)
-
- Structural requirement of isoflavonones for the inhibitory activity of interleukin-5
-
Sophoricoside isolated from Sophora japonica is a glycoside of isoflavonone as an inhibitor of interleukin (IL)-5. To identify structural requirements of this isoflavonone for its inhibitory activity against IL-5, isoflavonones, isoflavanones, and their glycosides were prepared and their inhibitory activity was tested against IL-5. Among them, 5-benzyloxy-3-(4-hydroxyphenyl)chromen-4-one (4b, 87.9% inhibition at 50 μM, IC50=15.3 μM) shows the most potent activity, comparable with that of sophoricoside. The important structural requirements of these isoflavonone analogs exhibiting the inhibitory activity against IL-5 were recognized as (1) planarity of chromen-4-one ring, (2) existence of phenolic hydroxyl at 4-position of B ring, and (3) introduction of benzyloxy at 5-position, which may act as a bulky group for occupying hydrophobic pocket in putative binding site. However the glucopyranosyl moiety of sophoricoside is not an essential motif for the activity.
- Jung, Sang-Hun,Cho, Soo-Hyun,Hung Dang, The,Lee, Jee-Hyun,Ju, Jung-Hun,Kim, Mi-Kyung,Lee, Seung-Ho,Ryu, Jae-Chun,Kim, Youngsoo
-
p. 537 - 545
(2007/10/03)
-
- Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase
-
Systematic simplification of the molecular structures of epicatechin gallate and epigallocatechin gallate to determine the minimum structural characteristics necessary for HIV-1 reverse transcriptase inhibition in vitro resulted in several compounds that strongly inhibited the native as well as the A17 double mutant (K103N Y181C) enzyme, which is normally insensitive to most known nonnucleoside inhibitors.
- Tillekeratne,Sherette,Grossman,Hupe,Hupe,Hudson
-
p. 2763 - 2767
(2007/10/03)
-
- Synthesis of 3-(2-benzyloxy-6-hydroxyphenyl)-1-methylpyrazoles by the reaction of chromones with methylhydrazine
-
The 3-(2-benzyloxy-6-hydroxyphenyl)-5-(methyl, phenyl or styryl)pyrazoles were prepared from the reaction of 2-(methyl, phenyl or styryl)chromones with methylhydrazine. The structure of these compounds has been determined by several nmr techniques, and the reaction mechanism is discussed.
- Pinto,Silva,Cavaleiro
-
p. 1629 - 1634
(2007/10/03)
-
- Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones
-
This invention relates to compounds of Formula I STR1 which are useful in association with a pharmaceutical carrier as antiatherosclerotic agents. In addition, various compounds of Formula I are useful inhibitors of cell proliferation.
- -
-
-
- Synthesis of (+/-)-Fistacacidin
-
Synthesis of fistacacidin and (+/-)-2,3-trans-5,4'-dimethoxyflavan-3-ol (XVII) are reported.Synthesis of XII, starting from monobenzyl ether of 2,6-dihydroxyacetophenone (I) involves the reacti
- Patil, A. D.,Deshpande, V. H.
-
p. 109 - 113
(2007/10/02)
-
- REGULATION OF ENZYMIC OXIDATION OF INDOLE-3-ACETIC ACID BY PHENOLS: STRUCTURE-ACTIVITY RELATIONSHIPS
-
Mono- and diphenols were tested for their effects on the decarboxylation of IAA catalysed by purified horseradish peroxidase (EC 1.11.1.7) in the presence or absence of 2,4-dichlorophenol (DCP).The number of hydroxyl groups and their position relative to each other and the nature and position of other substituents on the aromatic ring were found to affect the activity.Although the effects were complex, the following generalizations may be made. (1) Monophenols produce activation when no other cofactor is present. p-Substituted monophenols are more active than o- or m compounds.In the presence of DCP, the activity varies from slight activation to strong inhibition. (2) m-Diphenols also produce activation in the absence of other cofactors while o- and p-diphenols, with the exception of 3,4-dihydroxyacetophenone and 3,4-dihydroxypropiophenone, produce strong inhibition in the presence or absence of DCP.The o-diphenols are degraded in the IAA-oxidizing enzyme system and thus produce only a temporary inhibition. (3) m-Diphenols and 3,4-dihydroxyacetophenone produce a sustained inhibition in the presence of DCP. (4) Substitution at position 2 significantly alters the activity of m-diphenols. (5) o-Methylation alters the activity of most o-diphenols.In the absence DCP, o-methoxyphenols and certain other phenols such as 3,4-dihydroxyacetophenone and 2,6-dihydroxyacetophenone either promote or inhibit IAA oxidation depending on concentration.Key Word Index-Phenols; indole-3-acetic acid; IAA-oxidase; peroxidase.
- Lee, Tsung T.,Starratt, Alvin N.,Jevnikar, John J.
-
p. 517 - 524
(2007/10/02)
-