- Synthesis, solution studies and DFT investigation of a tripodal ligand with 3-hydroxypyran-4-one scaffold
-
Hydroxypyranones form very stable complexes and possess varied uses in medical applications. They are promising chelators for treating iron overload diseases as they form stable complexes with Fe3+. A novel tripodal ligand tris[(5-hydroxy-4-oxo
- Sharma, Shailza,Baral, Minati,Dash, Dibyajit,Kanungo
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p. 275 - 289
(2021/06/25)
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- ALA hybrid 3-hydroxypyridone derivative as well as preparation method and application thereof
-
The invention designs and synthesizes a novel anti-tumor active compound with iron chelating property and photosensitive activity based on the principles of reasonable drug design, drug-likeness and the like. The invention aims to provide a preparation me
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-
Paragraph 0112; 0114; 0160-0161
(2021/07/17)
-
- Bis-maltol-polyamine family: structural modifications at strategic positions. Synthesis, coordination and antineoplastic activity of two new ligands
-
Two new maltol-based ligands are presented,L1(N,N′-bis((3-hydroxy-6-methyl-4-pyron-2-yl)methyl)-N,N′-dimethylethylenediamine) andL2(N,N′-bis((3-hydroxy-6-hydroxymethyl-4-pyron-2-yl)methyl)-N,N′-dimethylethylenediamine). They were strategically designed by inserting a methyl or hydroxymethyl function at C6, to study the previously hypothesized involvement of that ring position in the anticancer properties and the peculiar metal coordination ability in aqueous solution already shown by this family of ligands. Solid state and solution studies revealed differences neither in the molecular conformation or crystal packing nor in the acid-base behavior compared with the precursor Malten. The introduced substituent groups seem to affect instead both the degradation time (ca.4-5 h forL1andL2vs.10 h for Malten) and the binding properties towards Cu(ii), Zn(ii) and Co(ii), log?Kvalues being the highest forL1within the series of the diamino-bis-maltol ligands. The introduction of -CH2OH at C6 is sufficient to impair the biological activity of the compound and is coherent with the hypothesized mechanism of action.
- Giorgi, Luca,Ambrosi, Gianluca,Paderni, Daniele,Conti, Luca,Amatori, Stefano,Romagnoli, Francesca,Rossi, Patrizia,Formica, Mauro,Macedi, Eleonora,Giorgi, Claudia,Paoli, Paola,Fanelli, Mirco,Fusi, Vieri
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p. 2659 - 2669
(2021/02/16)
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- A new “Mitsunobu homocoupling” reaction using aldol adducts of kojic acid
-
In this study, we attempted to carry out the Mitsunobu 1,4-elimination using the kojic acid analog 3, which carries a hydroxymethyl group on C-6 introduced by aldol condensation, to obtain an effective Michael acceptor 4. To the ethyl acetate solution of
- Azuma, Hideki,Morishima, Yasuhito,Nakaguro, Keijin,Kato, Reiko,Nagasaki, Takeshi
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- Quinazolinone-dihydropyrano[3,2-b]pyran hybrids as new α-glucosidase inhibitors: Design, synthesis, enzymatic inhibition, docking study and prediction of pharmacokinetic
-
A series of new quinazolinone-dihydropyrano[3,2-b]pyran derivatives 10A-L were synthesized by simple chemical reactions and were investigated for inhibitory activities against α-glucosidase and α-amylase. New synthesized compounds showed high α-glucosidase inhibition effects in comparison to the standard drug acarbose and were inactive against α-amylase. Among them, the most potent compound was compound 10L (IC50 value = 40.1 ± 0.6 μM) with inhibitory activity around 18.75-fold more than acarboase (IC50 value = 750.0 ± 12.5 μM). This compound was a competitive inhibitor into α-glucosidase. Our obtained experimental results were confirmed by docking studies. Furthermore, the cytotoxicity of the most potent compounds 10L, 10G, and 10N against normal fibroblast cells and in silico druglikeness, ADME, and toxicity prediction of these compounds were also evaluated.
- Sherafati, Maedeh,Mirzazadeh, Roghieh,Barzegari, Ebrahim,Mohammadi-Khanaposhtani, Maryam,Azizian, Homa,Sadegh Asgari, Mohammad,Hosseini, Samanesadat,Zabihi, Ebrahim,Mojtabavi, Somayeh,Ali Faramarzi, Mohammad,Mahdavi, Mohammad,Larijani, Bagher,Rastegar, Hossein,Hamedifar, Haleh,Hamed Hajimiri, Mir
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-
- Compound targeting ubiquitination degradation tyrosinase as well as preparation method and application thereof
-
A Tyr inhibitor kojic acid is covalently bound to a pomalidomide or VHL enzyme targeting ligand through a linkage chain to obtain a specific structure, and the preparation method is simple to operate and mild in condition. The generation of melanin is inhibited, the anti-melanin tumor effect is remarkable, and the safety period of vegetables and fruits can be remarkably prolonged. The compound targeted ubiquitination degradation tyrosinase provided by the invention has wide application prospects in medicine, food and cosmetics.
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-
Paragraph 0090-0092
(2021/09/08)
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- Pyrone compound as well as preparation method and application thereof
-
The invention provides a pyrone compound and a preparation method and application thereof. The molecular formula of the pyrone compound is C18H18N6O3S. The preparation method of the pyrone compound comprises the three steps of Schiff base synthesis, kojic
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-
Paragraph 0077-0078
(2021/11/10)
-
- Synthesis and Some Properties of New 5-Hydroxy-2-[(hetarylthio)methyl]-4H-pyran-4-ones
-
Abstract: The reaction of 2-thioxoazines with chlorokojic acid in the presence of KOH in DMF led to the formation of new hybrid molecules containing fragments of kojic acid and azaheterocycle linked by the SCH2 spacer. In silico prediction of b
- Aksenov, N. A.,Aksenova, I. V.,Dotsenko, V. V.,Guz, D. D.,Kindop, V. K.,Netreba, E. E.,Tebiev, D. T.
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p. 1629 - 1638
(2021/11/01)
-
- Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A: High-throughput virtual screening, synthesis and biological validation
-
Most cancer cells feature an altered glucose metabolism from oxidative phosphorylation to cytoplasmic glycolysis. Pyruvate dehydrogenase kinases (PDKs) and lactate dehydrogenase A (LDHA) play crucial roles in promotion of glycolysis, thus the inhibition of both enzymes is considered a promising strategy for developing of anticancer therapeutics. Herein, we describe the first discovery of series novel dual inhibitors targeting PDKs and LDHA. We identified 6 hits from a library database containing 485465 compounds through a high-throughput virtual screening assay. Hit-to-lead optimization enabled us to discover two compounds, namely 20e and 20k, which inhibited PDKs with IC50 values of 0.8, and 1.6 μM, respectively, and inhibited LDHA with IC50 values of 0.15 and 0.7 μM, respectively. Meanwhile, the two compounds reduced A549 cell proliferation with EC50 values of 13.2, and 15.7 μM. Furthermore, 20e and 20k decreased the lactate formation, and increased oxygen consumption, suggesting the two compounds modulated the glucose metabolic pathways in cancer cells.
- Xiang, Sichuan,Huang, Ding,He, Qiaolin,Li, Jie,Tam, Kin Yip,Zhang, Shao-Lin,He, Yun
-
supporting information
(2020/07/21)
-
- Adamantyl pyran-4-one derivatives and their in vitro antiproliferative activity
-
Abstract: Pyran-4-one (maltol, kojic acid and chlorokojic acid 1) esters of adamantan-1-ylacetic acid were prepared through efficient synthetic routes in good yields and evaluated for their in vitro antiproliferative activity on four cancer cell lines: K562 (chronic myelogenous leukemia), HeLa (cervical cancer), Caco-2 (colorectal adenocarcinoma) and NCI-H358 (bronchioalveolar carcinoma). The results indicate that the presence and the position of the adamantyl acyl group or chlorine atom are the necessary requirement for antitumor activity of pyranone systems. Derivatives of kojic acid with either free (compounds 1 and 8) or acylated 5-OH group (compounds 2 and 9) have shown good-to-moderate activity (IC50 values ranging from 13.1 to 43.0?μM) on all cell lines. Adamantyl kojic acid derivative 5 with a free OH group on the position 2 showed activity only on the K562 cell line. It seems that removal of halogen or adamantyl unit from position 2 elicits antileukemic activity, as observed in compound 5. The positive influence of the adamantyl unit was also observed on a 3-OH acylated derivative of maltol I which was also selectively active on the same cell line. 5-O-benzylated adamantyl compounds 6 and 7 and unmodified starting pyranones were found to be inactive. Antibacterial activity of compounds was also evaluated on S. aureus ATCC 13709, M. catarrhalis ATCC 23246, E. faecalis ATCC29212 and E. coli TolC-Tn10, but no activity was observed (MIC values 128–256?μg/mL). Graphical abstract: [Figure not available: see fulltext.]
- Perokovi?, Vesna Petrovi?,Car, ?eljka,Usenik, Andrea,Opa?ak-Bernardi, Teuta,Juri?, Andrea,Tomi?, Sr?anka
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p. 253 - 263
(2019/04/25)
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- An allomaltol derivative triggers distinct death pathways in luminal a and triple-negative breast cancer subtypes
-
Breast cancer is the most common cancer in women that shows a predisposition to metastasize to the distant organs. Kojic acid is a natural fungal metabolite exhibiting various biological activities. Compounds derived from kojic acid have been extensively studied and proved to demonstrate anti-neoplastic features on different cancer types. In the present study, allomaltol-structural analog of kojic acid and its seven derivatives including four novel compounds, have been synthesized, characterized and their possible impact on breast cancer cell viability was investigated. It was discovered that compound 5, bearing 3,4-dichlorobenzyl piperazine moiety, could decrease the viability of both MCF-7 and MDA-MB-231 cell lines distinctively. To ascertain the death mechanism, cells were subjected to different tests following the application of IC50 concentration of compound 5. Data obtained from lactate dehydrogenase activity and gene expression assays pointed out that necrosis had taken place predominantly in MDA-MB-231. On the other hand, in MCF-7 cells, the p53 apoptotic pathway was activated by overexpression of the pro-apoptotic TP53 and Bax genes and suppression of the anti-apoptotic Mdm-2 and Bcl-2 genes. Furthermore, Bax/Blc-2 ratio was escalated by 3.5 fold in the study group compared to the control. Compound 5 did not provoke drug resistance in MCF-7 cells since the Mdr-1 gene expression, drug efflux, and H2O2 content remained unaltered. As for MDA-MB-231 cells, only a 1.4 fold increase in the Mdr-1 gene expression was detected. These results indicate the advantage of the allomaltol derivative over the chemotherapeutic agents conventionally used for breast cancer treatment that can be highly toxic and mostly lead to drug resistance. Thus, this specific allomaltol derivative offers an alternative therapeutic approach for breast cancer which needs further investigation.
- Ercan,Oncul,Karakaya,Aytemir
-
-
- Rational design, synthesis and biological evaluation of novel multitargeting anti-AD iron chelators with potent MAO-B inhibitory and antioxidant activity
-
A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe3+ values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid-β1-42 (Aβ1-42) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.
- Bai, Renren,Gu, Jinping,Guo, Jianan,Jiang, Xiaoying,Lv, Yangjing,Mi, Zhisheng,Shi, Yuan,Xie, Yuanyuan,Yao, Chuansheng,Zhang, Changjun,Zhou, Tao
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-
- Tyrosinase inhibitor and application thereof
-
The invention provides a hydroxy-oxo-pyran-methyl ester compound and pharmaceutically-acceptable salts thereof. The hydroxy-oxo-pyran-methyl ester compound has a following structural formula as shownin the description, wherein the hydroxy-oxo-pyran-methyl ester compound is produced by using resveratrol and kojic acid as raw materials, has good tyrosinase inhibitor performance, is safe and effective, and can be widely applied for producing medicines, make-up or fruit and vegetable fresh-keeping agents.
- -
-
Paragraph 0039; 0088; 0090
(2019/09/14)
-
- The clean and mild synthesis, crystal structure, and intra-molecular hydrogen bond study of substituted new 4,8-dihydropyrano[3,2-b]-pyrans containing chlorokojic acid moiety
-
A safe, green and convenient process was developed for the synthesis of a novel group of 4,8-dihydropyrano[3,2-b]-pyrans by dialkyl acetylenedicarboxylates and alkyl isocyanides being trapped by chlorokojic acid in good to excellent yields at ambient temperature. Characterization of all structures was carried out by FT-IR and 1H and 13C NMR spectrometers, and two compounds were analyzed using X-ray diffraction technique. Crystal structures showed an intramolecular hydrogen bond and stacking of the dimeric (RS) molecules with the unit cell along the a-axis.
- Ojaghi Aghbash, Khadijeh,Noroozi Pesyan, Nader,Marandi, Ghasem,Dege, Necmi,?ahin, Ertan
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p. 4543 - 4554
(2019/05/21)
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- Dual-target anti-Alzheimer’s disease agents with both iron ion chelating and monoamine oxidase-B inhibitory activity
-
MAO-B leads to an increase in the levels of hydrogen peroxide and oxidative free radicals, which contribute to the aetiology of the AD. Thus, both iron ion chelators and MAO-B inhibitors can be used to treat AD. Taking the coumarin derivatives and hydroxypyridinones as the lead compounds, a series of dual-target hybrids were designed and synthesised by Click Chemistry. The compounds were biologically evaluated for their iron ion chelating and MAO-B inhibitory activity. Most of the compounds displayed excellent iron ion chelating activity and moderate to good anti-MAO-B activity. Compounds 27b and 27j exhibited the most potent MAO-B inhibitory activity, with IC50 values of 0.68 and 0.86 μM, respectively. In summary, these dual-target compounds have the potential anti-AD activity.
- Mi, Zhisheng,Gan, Bing,Yu, Sihang,Guo, Jianan,Zhang, Changjun,Jiang, Xiaoying,Zhou, Tao,Su, Jing,Bai, Renren,Xie, Yuanyuan
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p. 1489 - 1497
(2019/08/26)
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- Synthesis, computational molecular docking analysis and effectiveness on tyrosinase inhibition of kojic acid derivatives
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Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/methyl/morpholinomethylpiperidinyl- methyl/pyrrolidinylmethyl-4H-pyran-4-one structure (compounds 1–30)with inhibitory effects on tyrosinase enzyme were described. One-pot Mannich reaction was carried out by using kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in presence of formaline. Subsequently, cyclic amine (morpholine, piperidine and pyrrolidine)derivatives of the 6th-position of chlorokojic acid were obtained with nucleophilic substitutions in basic medium. The structures of new compounds were identified by FT-IR, 1H- and 13C NMR, ESI-MS and elemental analysis data. The potential mushroom tyrosinase inhibitory activity of the compounds were evaluated by the spectrophotometric method using L-DOPA as a substrate and kojic acid as the control agent. The potential inhibitory activity was also investigated in silico using molecular docking simulation method. Tyrosinase inhibitory action was significantly more efficacious for several compounds (IC50: 86.2–362.1 μM)than kojic acid (IC50: 418.2). Compound 3 bearing 3,4-dichlorobenzyl piperazine moiety was proven to have the highest inhibitory activity. The results of docking studies showed that according to the predicted conformation of compound 3 in the enzyme binding site, hydroxymethyl group provides a metal complex with copper ions and enzyme. Thus, this interaction explain the high inhibitory activities of the compounds 1, 3 and 4 possessing hydroxymethyl substituent supporting the mushroom assay results with docking studies. In accordance with the results, it is suggested that Mannich bases of kojic acid bearing substituted benzyl piperazine groups (compounds 1, 3, 4, 11, 13, 14, 23, 24, 28, and 29)could be promising antityrosinase agents. Additionally, considering the relationship between tyrosinase inhibitory activity results and molecular docking, a new tyrosinase inhibition mechanism can be proposed.
- Karakaya, Gül?ah,Türe, Asl?,Ercan, Ay?e,?ncül, Selin,Aytemir, Mutlu Dilsiz
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- TRIMETHOXY PHENYL COMPOUND AND COMPOSITION CONTAINING THE SAME FOR PROMOTING HAIR SPROUTING OR HAIR GROWTH
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The present invention relates to: a trimethoxy phenyl compound, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof; and a composition for promoting hair growth or hair restoration, containing the same as
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-
Paragraph 0075; 0077-0080
(2019/06/08)
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- 1,2,3-Triazole-based kojic acid analogs as potent tyrosinase inhibitors: Design, synthesis and biological evaluation
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A series of kojic acid-derived compounds 6a-p bearing aryloxymethyl-1H-1,2,3-triazol-1-yl moiety were designed by modifying primary alcoholic group of kojic acid as tyrosinase inhibitors. The target compounds 6a-p were synthesized via click reaction. All
- Ashooriha, Morteza,Khoshneviszadeh, Mehdi,Khoshneviszadeh, Mahsima,Moradi, Seyed Ershad,Rafiei, Alireza,Kardan, Mostafa,Emami, Saeed
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p. 414 - 422
(2018/11/21)
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- Cu(I)-catalyzed alkyne–azide ‘click’ cycloaddition (CuAAC): a clean, efficient, and mild synthesis of new 1,4-disubstituted 1H-1,2,3-triazole-linked 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile–crystal structure
-
Cu(I)-catalyzed alkyne–azide ‘click’ cycloaddition (CuAAC) is an important ‘‘click chemistry’’ reaction that is widely known in materials science, chemical biology, and pharmaceutical chemistry. The CuAAC reaction of terminal alkynes affords an efficient and mild production of triazolic 1,4-disubstituted compounds. In this work, a green and valuable method was introduced for the synthesis of the category of different new 1,4-disubstituted 1,2,3-triazole swapped with a 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-cyano moiety. These triazolic derivatives were produced by treatment of various 2-amino-6-(azidomethyl)-4,8-dihydropyrano[3,2-b]pyran-3-carbonitriles with phenylacetylene in the presence of CuI as a catalyst with excellent yields (because CuAAC is selective to 1,4-disubstituted triazole derivatives) in a green solvent (ethanol/water). All structures were evaluated by 13C, 1H NMR, and FT-IR spectroscopy and a compound was analyzed by crystallography (X-ray) technique.
- Ojaghi Aghbash, Khadijeh,Noroozi Pesyan, Nader,?ahin, Ertan
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p. 2079 - 2094
(2019/01/16)
-
- 1,3,4-thiadiazole-containing novel kojic acid derivative and application thereof
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The invention discloses a 1,3,4-thiadiazole-containing novel kojic acid derivative and application thereof. The structural formula is shown as a formula (I). The structural formula is as shown in thespecification. In the formula (I), the substituent group
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-
Paragraph 0014-0015
(2019/03/08)
-
- Development of novel human lactate dehydrogenase A inhibitors: High-throughput screening, synthesis, and biological evaluations
-
Human lactate dehydrogenase A (LDHA) plays a critical role in the glycolytic process, making the enzyme an ideal of anti-cancer drug target. Herein, we report the discovery of novel potent LDHA inhibitors by screening an in-house library. The hit-to-lead modification enabled us to identify compound 24c, which inhibited LDHA activity with an EC50 value of 90 nM, and reduced MiaPaCa-2 cancer cell proliferation with an IC50 value of 2.1 μM. In line with the in vitro anticancer activity, 24c suppressed the tumor growth at a dose of 10 mg/kg in a MiaPaCa-2 cells xenograft model, but with little effect to the mice weight. Moreover, 24c strongly inhibited MiaPaCa-2 cell colonies formation, induced MiaPaCa-2 cell apoptosis, and arrested MiaPaCa-2 cell cycle at G2 phase. In addition, the mitochondrial bioenergetics analysis suggested that 24c could reprogram cancer cell metabolic pathways from glycolysis to oxidation phosphorylation, which verified by decreasing the extracellular acidification rates and lactate formation, and increasing oxygen consumption rate in cancer cell. All these results indicate 24c is a promising metabolic modulator for the anticancer drug development.
- Zhou, Yuan,Tao, Pingde,Wang, Meigui,Xu, Peng,Lu, Wei,Lei, Pan,You, Qiuyun
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p. 105 - 115
(2019/05/27)
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- Synthesis, molecular modelling and biological studies of 3-hydroxy-pyrane-4-one and 3-hydroxy-pyridine-4-one derivatives as HIV-1 integrase inhibitors
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Background: Despite the progress in the discovery of antiretroviral compounds for treating HIV-1 infection by targeting HIV integrase (IN), a promising and well-known drug target against HIV-1, there is a growing need to increase the armamentarium against
- Sirous, Hajar,Fassihi, Afshin,Brogi, Simone,Campiani, Giuseppe,Christ, Frauke,Debyser, Zeger,Gemma, Sandra,Butini, Stefania,Chemi, Giulia,Grillo, Alessandro,Zabihollahi, Rezvan,Aghasadeghi, Mohammad R.,Saghaie, Lotfollah,Memarian, Hamid R.
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p. 755 - 770
(2019/11/02)
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- New fluorescent rosamine chelator showing promising antibacterial activity against Gram-positive bacteria
-
The restricted number of antibiotics to treat infections caused by common multidrug resistant bacterial pathogens in the clinical setting demands a continuous search for new molecules with antibacterial properties. Bacterial iron deprivation represents a
- Novais, ?ngela,Moniz, Tania,Rebelo, Ana Rita,Silva, Ana M.G.,Rangel, Maria,Peixe, Luísa
-
supporting information
p. 341 - 349
(2018/06/01)
-
- Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease
-
Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PAN endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PAN endonuclease, a class of highly active and selective fragments was developed that displays IC50 values 50 values of ~10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.
- Credille, Cy V.,Dick, Benjamin L.,Morrison, Christine N.,Stokes, Ryjul W.,Adamek, Rebecca N.,Wu, Nicholas C.,Wilson, Ian A.,Cohen, Seth M.
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p. 10206 - 10217
(2018/11/23)
-
- Novel Thiosulfate Derivative, Its Preparation Method and Cosmetic Composition Comprising the Same
-
The present invention refers to compound sulfate derivatives, its manufacturing method and including cosmetic composition active ingredient number [...] substrate. Thio sulfate derivatives of the present invention number and compound inhibiting tyrosinase activity billion number has a whitening effect through melanin billion, cosmetic composition can be used. (by machine translation)
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Paragraph 0094; 0096; 0097
(2018/07/28)
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- The clean synthesis and confirmatory structural characterization of new 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-cyano based on Kojic acid
-
Abstract: A valuable and clean method was developed for the synthesis of the group of different novel 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitriles containing a 2-aminopyran moiety by using of azido kojic acid and various 2-arylidinemalononitriles in the presence of NH4Cl as a catalyst in a green solvent (ethanol) with excellent yields. All structures were analyzed by FT-IR, 1H, 13C NMR spectroscopy, and representatively, one compound was analyzed by X-ray crystallography technique. Crystallographic analyses indicated that of this compound a dimer formed via two weak intermolecular hydrogen bonds with d(N···O) distances of 2.927?? and made a 14-membered ring with centrosymmetric (Ci) form. Graphical abstract: [Figure not available: see fulltext.].
- Aghbash, Khadijeh Ojaghi,Pesyan, Nader Noroozi,Notash, Behrouz
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p. 2059 - 2067
(2018/09/14)
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- NOVEL KOJIC ACID DERIVATIVES, PREPARATION METHOD THEREOF, AND COMPOSITIONS CONTAINING THE SAME FOR SKIN WHITENING
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PURPOSE: A kojic acid derivative and a cosmetic composition containing the same for skin whitening are provided to suppress melanogenesis and pigmentation with skin safety and to be applied to an external use skin formulation. CONSTITUTION: A kojic acid d
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Paragraph 0113-0115
(2018/04/12)
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- SALICYLIC ACID DERIVATIVE, METHOD FOR PREPARING SAME, AND COSMETIC COMPOSITION FOR WHITENING COMPRISING SAME
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The present invention relates to a novel salicylic acid derivative, a method for preparing the same, and a cosmetic composition for whitening having the same. The compound exhibits a skin whitening effect by acting on tyrosinase, which is a melanin produc
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-
Paragraph 0066
(2019/01/10)
-
- NOVEL HYDROXYL PYRANONE COMPOUND, METHOD FOR PRODUCING SAME, AND COSMETICS COMPOSITION COMPRISING COMPOUND
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The present invention relates to a novel hydroxyl pyranone compound, a method for producing same, and a cosmetic composition having the compound. The hydroxyl pyranone compound according to the present invention exhibits markedly improved effectiveness co
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-
Paragraph 0048-0054
(2019/01/10)
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- Design, synthesis and biological evaluation of 2-substituted 3-hydroxy-6-methyl-4H-pyran-4-one derivatives as Pseudomonas aeruginosa biofilm inhibitors
-
Drug-resistant bacteria associated with biofilm formation are rapidly on the rise, requiring novel therapeutic options to combat biofilm induced drug-resistance. In this study, a class of 3-hydroxy-2-(phenylhydroxy-methyl)-6-methyl-4H-pyran-4-one derivati
- Li, Yi-Bin,Liu, Jun,Huang, Zhi-Xing,Yu, Jia-Hui,Xu, Xiao-Fang,Sun, Ping-Hua,Lin, Jing,Chen, Wei-Min
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p. 753 - 766
(2018/10/15)
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- Kojyl cinnamate esters are peroxisome proliferator-activated receptor α/γ dual agonists
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Adiponectin is an adipocytokine with insulin-sensitizing, anti-inflammatory, anti-atherosclerotic, and anti-aging properties. Compounds with the ability to promote adiponectin secretion are of interest for the development of anti-aging drugs to improve skin-aging phenotypes. In the phenotypic assay to measure adiponectin secretion during adipogenesis in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs), kojyl cinnamate ester derivatives increased adiponectin secretion. A target identification study showed that the kojyl cinnamate ester derivatives competitively bound to peroxisome proliferator-activated receptor α/γ (PPARα/γ). The upregulation of adiponectin production induced by kojyl cinnamate ester derivatives was significantly correlated with PPARα and PPARγ binding activities. Kojyl cinnamate ester derivatives significantly increased the transcription of genes encoding cholesterol and fatty acid synthesizing enzymes in hAT-MSCs. Notably, the kojyl cinnamate esters upregulated the gene transcription of lipid metabolic enzymes in human epidermal keratinocytes, which are important in the integrity of skin permeability barrier. In addition, the kojyl cinnamate esters that function as PPARα/γ dual modulators inhibited ultraviolet B irradiation-induced inflammation in human epidermal keratinocytes. Therefore, kojyl cinnamate ester derivatives are a novel class of PPARα/γ dual agonists with the potential to improve skin-aging phenotypes.
- Kim, Sae On,Han, Yujia,Ahn, Sungjin,An, Seungchan,Shin, Jeayoung C.,Choi, Hyunjung,Kim, Hyoung-June,Park, Nok Hyun,Kim, Yong-Jin,Jin, Sun Hee,Rho, Ho Sik,Noh, Minsoo
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p. 5654 - 5663
(2018/10/24)
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- COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
-
There are provided inter alia metalloenzyme inhibitors, such as inhibitors of influenza A RNA dependent RNA polymerase PA subunit endonuclease, and methods of synthesis and use of the same.
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-
Paragraph 0495; 0588
(2017/09/27)
-
- NOVEL HYDROXY PYRANONE DERIVATIVE, PREPARATION METHOD THEREOF, AND COSMETIC COMPOSITION COMPRISING THE SAME
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The present invention relates to a novel hydroxypyranone compound which is represented by chemical formula 1, a production method thereof, and a cosmetic composition containing the same. According to the present invention, the novel hydroxypyranone compou
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-
Paragraph 0060; 0062
(2017/07/14)
-
- Synthesis of the Conjugate of Cytisine and Kojic Acid
-
N-(5-Hydroxypyran-4-on-2-ylmethyl)cytisine was synthesized.
- Muzychuk,Garazd
-
p. 517 - 518
(2017/08/30)
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- Synthesis of some novel 1,2,3-triazole derivatives containing kojic acid moiety and evaluation for their antioxidant activity
-
Abstract: A series of novel 1,2,3-triazole derivatives containing kojic acid moiety were synthesized by 1,3-dipolar cycloaddition reaction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one and 2-(azidomethyl)-5-benzyloxy-4H-pyran-4-one with different alkynes in
- Saraei, Mahnaz,Ghasemi, Zarrin,Dehghan, Gholamreza,Hormati, Marhamat,Ojaghi, Khadijeh
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p. 917 - 923
(2017/04/14)
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- A mild method for the replacement of a hydroxyl group by halogen. 1. Scope and chemoselectivity
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α-Chloro-, bromo- and iodoenamines, which are readily prepared from the corresponding isobutyramides have been found to be excellent reagents for the transformation of a wide variety of alcohols or carboxylic acids into the corresponding halides. Yields are high and conditions are very mild thus allowing for the presence of sensitive functional groups. The reagents can be easily tuned allowing therefore the selective monohalogenation of polyhydroxylated molecules. The scope and chemoselectivity of the reactions have been studied and reaction mechanisms have been proposed.
- Munyemana, Fran?ois,George, Isabelle,Devos, Alain,Colens, Alain,Badarau, Eduard,Frisque-Hesbain, Anne-Marie,Loudet, Aurore,Differding, Edmond,Damien, Jean-Marie,Rémion, Jeanine,Van Uytbergen, Jacqueline,Ghosez, Léon
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p. 420 - 430
(2015/12/31)
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- PYRIDOPYRAZINE COMPOUNDS AND THEIR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF INFLUENZA
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The present invention relates to a compound having the general formula (V), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, w
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Paragraph 0149; 0153
(2016/01/30)
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- Fragment-Based Identification of Influenza Endonuclease Inhibitors
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The influenza virus is responsible for millions of cases of severe illness annually. Yearly variance in the effectiveness of vaccination, coupled with emerging drug resistance, necessitates the development of new drugs to treat influenza infections. One a
- Credille, Cy V.,Chen, Yao,Cohen, Seth M.
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supporting information
p. 6444 - 6454
(2016/07/26)
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- Systematic comparison of the mono-, dimethyl-and trimethyl 3-hydroxy-4(1H)-pyridones-Attempted optimization of the orally active iron chelator, deferiprone
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A range of close analogues of deferiprone have been synthesised. The group includes mono-, di-and trimethyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe3+ values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NHcontaining hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis.
- Xie, Yuan-Yuan,Lu, Zidong,Kong, Xiao-Le,Zhou, Tao,Bansal, Sukhi,Hider, Robert
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p. 132 - 140
(2016/04/05)
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- Organometallic complexes of (thio)allomaltol-based Mannich-products: Synthesis, stability and preliminary biological investigations
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Abstract Organometallic complexes with (thio)pyrone-based ligands have been shown to possess promising cytotoxic properties. To extend the class of potential metallodrugs, the (thio)pyrone backbone was modified via Mannich reaction with morpholine, N-methylpiperazine and piperidine as cyclic amine. The ligands and organometallic complexes were characterized by means of 1D and 2D NMR, ESI MS and also in one case by X-ray diffraction analysis. Due to the high aqueous solubility, the behavior and stability in aqueous solution of the synthesized complexes was studied by 1H NMR spectroscopy. In addition, the influence of these modifications on cytotoxicity in human cancer cell lines was investigated by means of the MTT assay.
- Schmidlehner, Melanie,Pichler, Verena,Roller, Alexander,Jakupec, Michael A.,Kandioller, Wolfgang,Keppler, Bernhard K.
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- Synthesis and Biological Evaluation of Kojic Acid Derivatives Containing 1,2,4-triazole as Potent Tyrosinase Inhibitors
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A series of 5-substituted-3-[5-hydroxy-4-pyrone-2-yl-methymercapto]-4-amino-1,2,4-triazole derivatives were synthesized by nucleophilic substitution reaction of 5-hydroxy-2-chloromethyl -4H-pyran-4-one with 5-substituted-3-mercapto-4-amino-1,2,4-triazole,
- Xie, Wenlin,Zhang, Jingai,Ma, Xiaojing,Yang, Wenqian,Zhou, Ying,Tang, Xufu,Zou, Yan,Li, Hui,He, Jingjing,Xie, Shimin,Zhao, Yunhui,Liu, Fengping
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p. 1087 - 1092
(2015/10/28)
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- SMALL MOLECULE ANTAGONISTS OF THE APELIN RECEPTOR FOR THE TREATMENT OF DISEASE
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The present disclosure relates to compounds and methods for treating a disease mediated by apelin.
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Paragraph 0152-0153
(2014/02/15)
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- CONJUGATES AND THEIR USES IN MOLECULAR IMAGING
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The present invention relates to bifunctional compounds, the bifunctional compounds for use in molecular imaging and therapy, methods of molecular imaging using the bifunctional compounds and kits including the bifunctional compounds for use molecular imaging. The bifunctional compounds have a tripodal hydroxypyridinone chelating portion and may be conjugated to a targeting group so that the compounds target specific cells or tissues in a subject.
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Paragraph 0099
(2014/03/24)
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- PYRIDONE DERIVATIVES AND THEIR USE IN THE TREATMENT, AMELORIATION OR PREVENTION OF A VIRAL DISEASE
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The present invention relates to a compound having the general formula (II), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, codrug, cocrystal, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which are useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
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Paragraph 0117; 0118
(2014/07/22)
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- Synthesis, characterization, and antimicrobial activity of kojic acid grafted chitosan oligosaccharide
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A novel water-soluble chitosan oligosaccharide (COS) derivative, chitosan oligosaccharide/kojic acid grafts assigned as COS/KA, was prepared by using the selective partial alkylation of N-benzylidene COS and chlorokojic acid in the presence of dimethyl sulfoxide (DMSO) and pyridine (Py). The derivative was characterized by UV-vis spectroscopy, FTIR, 1H NMR, TGA, SEM, and XRD techniques, which showed that the alkylation reaction took place at the C-6 and C-3 positions of COS. The results showed that the degree of substitution (DS) for COS/KA was from 0.38 to 1.21, and the product exhibited an excellent solubility in organic solvents and distilled water. The antibacterial results indicated that the antibacterial activity of COS/KA was strengthened relative to COS with the increase of DS for Staphylococcus aureus, Escherichia coli, Aspergillus niger and Saccharomyces cerevisiae. These findings provide important supports for developing new antibacterial agents and expand the scope of application of COS in the food industry.
- Liu, Xiaoli,Xia, Wenshui,Jiang, Qixing,Xu, Yanshun,Yu, Peipei
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p. 297 - 303
(2014/01/23)
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- Kojyl cinnamate ester derivatives promote adiponectin production during adipogenesis in human adipose tissue-derived mesenchymal stem cells
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The subcutaneous fat tissue mass gradually decreases with age, and its regulation is a strategy to develop anti-aging compounds to ameliorate the photo-aging of human skin. The adipogenesis of human adipose tissue-mesenchymal stem cells (hAT-MSCs) can be
- Rho, Ho Sik,Hong, Soo Hyun,Park, Jongho,Jung, Hyo-Il,Park, Young-Ho,Lee, John Hwan,Shin, Song Seok,Noh, Minsoo
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p. 2141 - 2145
(2014/05/06)
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- Identification of the structural determinants for anticancer activity of a ruthenium arene peptide conjugate
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Organometallic Ru(arene)-peptide bioconjugates with potent in vitro anticancer activity are rare. We have prepared a conjugate of a Ru(arene) complex with the neuropeptide [Leu5]-enkephalin. [Chlorido(η 6-p-cymene)(5-oxo-κO-2-{(4-[(N-tyrosinyl-glycinyl-glycinyl- phenylalanyl-leucinyl-NH2)propanamido]-1H-1,2,3-triazol-1-yl)methyl}- 4H-pyronato-κO)ruthenium(II)] (8) shows antiproliferative activity in human ovarian carcinoma cells with an IC50 value as low as 13 μM, whereas the peptide or the Ru moiety alone are hardly cytotoxic. The conjugation strategy for linking the Ru(cym) (cym=η6-p-cymene) moiety to the peptide involved N-terminal modification of an alkyne-[Leu5]- enkephalin with a 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one linker, using Cu I-catalyzed alkyne-azide cycloaddition (CuAAC), and subsequent metallation with the Ru(cym) moiety. The ruthenium-bioconjugate was characterized by high resolution top-down electrospray ionization mass spectrometry (ESI-MS) with regard to peptide sequence, linker modification and metallation site. Notably, complete sequence coverage was obtained and the Ru(cym) moiety was confirmed to be coordinated to the pyronato linker. The ruthenium-bioconjugate was analyzed with respect to cytotoxicity-determining constituents, and through the bioconjugate models [{2-(azidomethyl)-5-oxo- κO-4H-pyronato-κO}chloride (η6-p-cymene)ruthenium(II) ] (5) and [chlorido(η6-p-cymene){5-oxo-κO-2-([(4- (phenoxymethyl)-1H-1,2,3-triazol-1-yl]methyl)-4H-pyronato-κO}ruthenium(II) ] (6) the Ru(cym) fragment with a triazole-carrying pyronato ligand was identified as the minimal unit required to achieve in vitro anticancer activity. Copyright
- Meier, Samuel M.,Novak, Maria,Kandioller, Wolfgang,Jakupec, Michael A.,Arion, Vladimir B.,Metzler-Nolte, Nils,Keppler, Bernhard K.,Hartinger, Christian G.
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p. 9297 - 9307
(2013/07/26)
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- Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid derivatives
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A series of novel Mannich bases of chlorokojic acid (2-chloromethyl-5- hydroxy-4H-pyran-4-one) were synthesized and their biological activities were investigated. Anticonvulsant activity results according to phase-I tests of Antiepileptic Drug Development (ADD) Program revealed that compound 13 was the most effective one at 4h against subcutaneous pentylenetetrazole (scPTZ)-induced seizure test. Antimicrobial activities were evaluated in vitro against bacteria and fungi by using broth microdilution method. The antitubercular activities against Mycobacterium tuberculosis and M. avium were discussed with Resazurin microplate assay (REMA). The antimicrobial activity results indicated that compounds 1 and 12 (MIC: 8-16 g/mL) showed higher activity against Gram negative bacteria while compound 12 had MIC: 4-16 g/mL against Gram positive bacteria. Compound 1 was the most active one with MIC values of 8-32 g/mL against fungi. Mannich bases also exhibit significant antitubercular activity in a MIC range of 4 to 32 g/mL, especially compound 18 against M. avium.
- Karakaya, Guelsah,Aytemir, Mutlu Dilsiz,Oezcelik, Berrin,Calis, Uensal
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p. 627 - 638
(2013/05/21)
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