- An Aurone-derived Low-molecular-weight Fluorescence Probe for the Detection of Hg2+ in Aqueous Solution and Living Cells
-
A low-molecular-weight fluorescent probe 1 (M.W.?=?238.24) based on aurone was synthesized, and its application in fluorescent detection of Hg2+ in aqueous solution and living cells was reported. It exhibited an “on–off” fluorescent response to
- Zhang, Min,Bao, Yong-Tuan,Yang, Wenbo,Xiao, Hui-Feng,Han, Zhi-Xiang,Wu, Xiangyang,Yang, Liuqing
-
-
Read Online
- Photochemical activities of polymers with aurone fragment
-
In this work we report preliminary results obtained for methacrylic polymers incorporating aurone side-group as photochemical active molecule. The aurone polymers were obtained by a three-step synthetic approach: (2Z)-6-hydroxy-2-(4-R-benzyliden)-1-benzofuran-3(2H)-ones were synthesized by using condensation reation of 6-hydroxybenzofuran-3-one with benzaldehydes; then methacrylate monomers were synthesized by reaction the alcohols with methacryloyl chloride; and the polymers were synthesized by free radical polymerization. Polymers were characterized by 1HNMR spectroscopy and DSC techniques. Their physicochemical properties are determined by absorption, fluorescence excitation and emission spectroscopies.
- Smokal, Vitaliy,Kharchenko, Oksana,Karabets, Yuriy,Iukhymenko, Nataliia,Kysil, Andrii,Krupka, Oksana,Kolendo, Aleksiy
-
-
Read Online
- Synthesis, characterization, and anticancer effect of trifluoromethylated aurone derivatives
-
A series of trifluoromethylated aurone derivatives were synthesized, and the structure of 6-hydroxy- 4-trifluoromethylated aurone was determined by single crystal X-ray analysis. Their anticancer activities against leucocythemia (HL-60) and colorectal ade
- Zheng, Xing,Wang, Hui,Liu, Yun-Mei,Yao, Xu,Tong, Min,Wang, Yu-Hong,Liao, Duan-Fang
-
-
Read Online
- Design, synthesis, and biological evaluation of a novel dual peroxisome proliferator-activated receptor alpha/delta agonist for the treatment of diabetic kidney disease through anti-inflammatory mechanisms
-
Diabetic kidney disease (DKD) is a major feature of the final stage of nearly all cause types of diabetes mellitus (DM). To date, few safe and effective drugs are available to treat. Peroxisome proliferator-activated receptors (PPARs), comprised of three members: PPAR-α, PPAR-δ and PPAR-γ, play a protective role in the DKD through glycemic control and lipid metabolism, whereas systemic activation of PPAR-γ causes serious side-effects in clinical trials. GFT505 is a dual PPAR-α/δ agonist, and the selectivity against PPAR-γ is still to be improved. Sulfuretin has been shown to suppress the expression of PPAR-γ and improve the pathogenesis of diabetic complications. In this study, by hybridizing the carboxylic acid of GFT505 and the parent nucleus of sulfuretin, we pioneeringly designed and synthetized a series of novel dual PPAR-α/δ agonists, expecting to provide a better benefit/risk ratio for PPARs. Of all the synthesized compounds, compound 12 was identified with highly activity on PPAR-α/δ and higher selectivity against PPAR-γ than that of GFT505 (EC50: hPPAR-α: 0.26 μM vs.0.76 μM; hPPAR-δ: 0.50 μM vs.0.73 μM; hPPAR-γ: 4.22 μM vs.2.79 μM). The molecular docking studies also depicted good binding affinity of compound 12 for PPAR-α and PPAR-δ compared to GFT505. Furthermore, compound 12 exhibited an evidently renoprotective effect on the DKD through inhibiting inflammatory process, which might at least partly via JNK/NF-κB pathways in vivo and in vitro. Overall, compound 12 hold therapeutic promise for DKD.
- Liu, Kai,Zhao, Xing,Qi, Xue,Hou, Dong-Liang,Li, Hao-Bin,Gu, Yu-Hao,Xu, Qing-Long
-
-
- Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB
-
Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm, whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC99 values ranging from 0.4 to 2.0 μm. In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.
- Campani?o, André,Carrasco, Marta P.,Njoroge, Mathew,Seldon, Ronnett,Chibale, Kelly,Perdig?o, Jo?o,Portugal, Isabel,Warner, Digby F.,Moreira, Rui,Lopes, Francisca
-
p. 1537 - 1546
(2019/08/02)
-
- Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells
-
Abstract: An efficient method for regioselective synthesis of C-7 Mannich bases of 6-hydroxyaurones was accomplished by the N,N-dialkylaminomethylation using aminals prepared from dimethylamine, dipropylamine, bis(2-methoxyethyl)amine, N-methylbutylamine, N-methylbenzylamine, morpholine, piperidine, and 1-methylpiperazine. Further transformation of 7-(N,N-dialkylamino)methyl group in these aurones led to formation of C-7 acetoxymethyl and methoxymethyl derivatives of 6-hydroxyaurones, some of which showed promising inhibition of PC-3 prostate cancer cell proliferation in the high nanomolar to low micromolar range that exceeded that of cisplatin. Graphical abstract: Compound 12c (R3 = Ac, Ar = 3,4-OMePh) displays 75% inhibition of PC-3 prostate cancer cells proliferation at 300 nM concentration.[Figure not available: see fulltext.]
- Popova, Antonina V.,Frasinyuk, Mykhaylo S.,Bondarenko, Svitlana P.,Zhang, Wen,Xie, Yanqi,Martin, Zachary M.,Cai, Xianfeng,Fiandalo, Michael V.,Mohler, James L.,Liu, Chunming,Watt, David S.,Sviripa, Vitaliy M.
-
p. 2443 - 2456
(2018/08/16)
-
- Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase
-
Xanthine oxidase is a potential target for treatment of hyperuricemia and gout. In this study, a number of A- and B-ring carboxylated aurone derivatives were synthesized and evaluated for their ability to inhibit xanthine oxidase in vitro. According to the results obtained, two different ranges of inhibitory activity were observed. The aurones with carboxylic acid group at the 4′-position of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar range. The effects of these compounds were about 50 fold higher than of A-ring modified aurones with carboxymethoxy group at the 6-position. The binding modes of the carboxylated aurones in the active site of xanthine oxidase were explained using molecular docking calculations.
- Muzychka, Oksana V.,Kobzar, Oleksandr L.,Popova, Antonina V.,Frasinyuk, Mykhaylo S.,Vovk, Andriy I.
-
p. 3606 - 3613
(2017/06/13)
-
- Synthesis and Biological Activities of 6-Hydroxyaurone Derivatives
-
A series of 6-hydroxyaurone derivatives were synthesized in satisfactory yields and characterized by IR, 1H NMR, 13C NMR, and HRMS or elemental analysis. The structure of compound 3e was further confirmed by X-ray crystal analysis. B
- Bao, Yong-Tuan,Zhang, Min,Li, Ting,Xiao, Hui-Feng,Zhao, Ting,Xu, Xiao-Hua,Yang, Liu-Qing
-
p. 637 - 642
(2016/04/19)
-
- Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity
-
A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold. Additionally, Mannich-base derivatives, containing a 7-aminomethyl-6-hydroxy substitution pattern at ring A, were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC 50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2, two validated targets expressed during the blood stage of P. falciparum infection and functional in digestive vacuole of the parasite. Overall, this study highlight (i) the usefulness of aurones as platforms for synthetic procedures using palladium catalyzed protocols to rapidly deliver lead compounds for further optimization and (ii) the potential of novel aurone derivatives as promising antimalarial compounds.
- Carrasco, Marta P.,Newton, Ana S.,Gon?alves, Lídia,Góis, Ana,Machado, Marta,Gut, Jiri,Nogueira, Fátima,H?nscheid, Thomas,Guedes, Rita C.,Dos Santos, Daniel J.V.A.,Rosenthal, Philip J.,Moreira, Rui
-
p. 523 - 534
(2014/05/20)
-
- Investigation of binding-site homology between mushroom and bacterial tyrosinases by using aurones as effectors
-
Tyrosinase is a copper-containing enzyme found in plants and bacteria, as well as in humans, where it is involved in the biosynthesis of melanin-type pigments. Tyrosinase inhibitors have attracted remarkable research interest as whitening agents in cosmetology, antibrowning agents in food chemistry, and as therapeutics. In this context, commercially available tyrosinase from mushroom (TyM) is frequently used for the identification of inhibitors. This and bacterial tyrosinase (TyB) have been the subjects of intense biochemical and structural studies, including X-ray diffraction analysis, and this has led to the identification of structural homology and divergence among enzymes from different sources. To better understand the behavior of potential inhibitors of TyM and TyB, we selected the aurone family - previously identified as potential inhibitors of melanin biosynthesis in human melanocytes. In this study, a series of 24 aurones with different hydroxylation patterns at the A- and B-rings were evaluated on TyM and TyB. The results show that, depending on the hydroxylation pattern of A- and B-rings, aurones can behave as inhibitors, substrates, and activators of both enzymes. Computational analysis was performed to identify residues surrounding the aurones in the active sites of both enzymes and to rationalize the interactions. Our results highlight similarities and divergence in the behavior of TyM and TyB toward the same set of molecules. A lighter future: Aurones have been identified as inhibitors of melanin biosynthesis. In this study, 24 aurones were evaluated on mushroom and bacterial tyrosinases (TyM and TyB). The compounds behaved as inhibitors, substrates, or activators of both enzymes. Our results highlight similarities and differences in behavior between TyM and TyB with the same set of molecules.
- Haudecoeur, Romain,Gouron, Aurelie,Dubois, Carole,Jamet, Helene,Lightbody, Mark,Hardre, Renaud,Milet, Anne,Bergantino, Elisabetta,Bubacco, Luigi,Belle, Catherine,Reglier, Marius,Boumendjel, Ahcene
-
p. 1325 - 1333
(2014/06/24)
-
- Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
-
The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity.
- Lee, Chong-Yew,Chew, Eng-Hui,Go, Mei-Lin
-
experimental part
p. 2957 - 2971
(2010/09/03)
-
- Discovery of benzylidenebenzofuran-3(2H)-one (aurones) as inhibitors of tyrosinase derived from human melanocytes
-
Tyrosinase is a copper-dependent enzyme which converts L- tyrosine to dopaquinone and is involved in different biological processes such as melanogenesis and skin hyperpigmentation. The purpose of this study was to investigate naturally occurring aurones (Z-benzylidenebenzofuran-3(2H)-one) and analogues as human tyrosinase inhibitors. Several aurones bearing hydroxyl groups on A-ring and different substituents on B-ring were synthesized and evaluated as inhibitors of human melanocyte-tyrosinase by an assay which measures tyrosinase-catalyzed L-Dopa oxidation. We found that unsubstituted aurones were weak inhibitors; however, derivatives with two or three hydroxyl groups preferably at 4,6 and 4′ positions are able to induce significant tyrosinase inhibition. The most potent aurone was found to be the naturally occurring 4,6,4′-trihydroxyaurone which induces 75% inhibition at 0.1 mM concentration and is highly effective when compared to kojic acid, one of the best tyrosinase inhibitors known so far (the latter is completely inactive at such concentrations). Active aurones are devoid of toxic effects as shown by in vivo studies.
- Okombi, Sabrina,Rival, Delphine,Bonnet, Sébastien,Mariotte, Anne-Marie,Perrier, Eric,Boumendjel, Ahcène
-
p. 329 - 333
(2007/10/03)
-
- A method of cosmetic depigmentation care by applying at least one aurone
-
At least one aurone or a natural or synthetic derivative of aurone, or an analogue of aurone, in which the independent phenyl ring can be substituted by a heterocycle of pyrrole, imidazole, triazole, pyridine, furan, or thiophene type, is disclosed as a cosmetic agent, or as an active substance, for the manufacture either of a cosmetic composition, or of a pharmaceutical composition, notably a dermatological composition, having a melanogenesis-inhibiting activity or a depigmenting activity, or an anti-tyrosinase activity.
- -
-
Page/Page column 9-10
(2008/06/13)
-
- ALUMINA-MEDIATED CONDENSATION. A SIMPLE SYNTHESIS OF AURONES
-
A simple and high yielding synthesis of aurones (2-phenylmethylene-3(2H)-benzofuranones) is described which occurs under mild conditions on alumina surface using readily available benzofuranones and arylaldehydes.Key Words: Aurones; 2-Phenylmethylene-3(2H)-benzofuranones; Solid Surface; Alumina
- Varma, Rajender S.,Varma, Manju
-
p. 5937 - 5940
(2007/10/02)
-
- Synthesis of 2-(p-Chlorobenzyl)-3-aryl-6-methoxybenzofurans as Selective Ligands for Antiestrogen-Binding Sites. Effects on Cell Proliferation and Choresterol Synthesis
-
A series of nonsteroidal compounds, 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans derived from the 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones has been synthesized.The key steps in the synthesis were reactions of 2-(p-chlorobenzyl)-6-methoxy-3(2H)-benzofuranones with the arylorganometallic reagents followed by dehydration of the resulting carbinols.The benzofurans are ligands for antiestrogen-binding sites (AEBS) and display no significant interaction with the estrogen receptor (ER).All bind to AEBS with equivalent or greater affinity than tamoxifen.These compounds decrease thymidine incorporation in AEBS-containing EL4 lymphoid cells and MCF7 breast cancer cells in a concentration-dependent manner between 10-8 and 10-6 M and are generally more inhibitory than tamoxifen.In contrast, they have no effect on thymidine incorporation by an AEBS-deficient variant of the MCF7 cell line, RTx6.The present findings of (1) selective and high affinity binding of the benzofurans to AEBS, (2) their concentration-dependent inhibition of thymidine incorporation in AEBS-containing cells, and (3) their lack of antiproliferative effect in an AEBS-deficient cell line suggest a functional role for AEBS in mediating the antigrowth effect of these compounds.Two of the more active benzofuran compounds also significantly inhibited de novo cholesterol biosynthesis in EL4 cells which lack ER.This effect could be obtained after 5 h of treatment and preceded significant loss of cell viability.This is the first demonstration that selective ligands of AEBS (other than the known nonsteroidal antiestrogens) interfere with cholesterol biosynthesis - an action that may contribute to their antigrowth effect.
- Teo, Chin Chin,Kon, Oi Lian,Sim, Keng Yeow,Ng, Siu Choon
-
p. 1330 - 1339
(2007/10/02)
-