1080-12-2Relevant articles and documents
Synthesis and cytotoxic evaluation of monocarbonyl curcuminoids and their pyrazoline derivatives
Van de Walle, Tim,Theppawong, Atiruj,Grootaert, Charlotte,De Jonghe, Steven,Persoons, Leentje,Daelemans, Dirk,Van Hecke, Kristof,Van Camp, John,D’hooghe, Matthias
, p. 2045 - 2051 (2019)
Abstract: A small set of structurally different monocarbonyl curcuminoids was prepared and screened for cytotoxic activity. In particular, bis-3-methoxy-4-hydroxy- and bis-4-methoxyphenyl-substituted monocarbonyls were synthesized and transformed into the corresponding three-dimensional N-acetylpyrazoline derivatives. In addition, a non-symmetrical indole-based monocarbonyl curcumin was prepared as well. Preliminary cytotoxic evaluation revealed significant effects for 4-hydroxy (pyrazoline) monocarbonyl curcuminoids, whereas the non-phenolic variants displayed rather poor activity. Graphic abstract: [Figure not available: see fulltext.].
Small molecules interacting with α-synuclein: Antiaggregating and cytoprotective properties
Marchiani, Anna,Mammi, Stefano,Siligardi, Giuliano,Hussain, Rohanah,Tessari, Isabella,Bubacco, Luigi,Delogu, Giovanna,Fabbri, Davide,Dettori, Maria A.,Sanna, Daniele,Dedola, Sonia,Serra, Pier A.,Ruzza, Paolo
, p. 327 - 338 (2013)
Curcumin, a dietary polyphenol, has shown a potential to act on the symptoms of neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, as a consequence of its antioxidant, anti-inflammatory and anti-protein aggregation properties. Unfortunately, curcumin undergoes rapid degradation at physiological pH into ferulic acid, vanillin and dehydrozingerone, making it an unlikely drug candidate. Here, we evaluated the ability of some curcumin by-products: dehydrozingerone (1), its O-methyl derivative (2), zingerone (3), and their biphenyl analogues (4-6) to interact with α-synuclein (AS), using CD and fluorescence spectroscopy. In addition, the antioxidant properties and the cytoprotective effects in rat pheochromocytoma (PC12) cells prior to intoxication with H2O 2, MPP+ and MnCl2 were examined while the Congo red assay was used to evaluate the ability of these compounds to prevent aggregation of AS. We found that the biphenyl zingerone analogue (6) interacts with high affinity with AS and also displays the best antioxidant properties while the biphenyl analogues of dehydrozingerone (4) and of O-methyl-dehydrozingerone (5) are able to partially inhibit the aggregation process of AS, suggesting the potential role of a hydroxylated biphenyl scaffold in the design of AS aggregation inhibitors.
Retro-curcuminoids as mimics of dehydrozingerone and curcumin: Synthesis, NMR, X-ray, and cytotoxic activity
Obregón-Mendoza, Marco A.,Estévez-Carmona, María Mirian,Hernández-Ortega, Simón,Soriano-García, Manuel,Ramírez-Apan, María Teresa,Orea, Laura,Pilotzi, Hugo,Gnecco, Dino,Cassani, Julia,Enríquez, Raúl G.
, (2017)
Curcumin and its derivatives have been extensively studied for their remarkable medicinal properties, and their chemical synthesis has been an important step in the optimization of well-controlled laboratory production. A family of new compounds that mimic the structure of curcumin and curcuminoids, here named retro-curcuminoids (7-14), was synthesized and characterized using 1D 1H- and 13C-NMR, IR, and mass spectrometry; the X-ray structure of 7, 8, 9, 10, 12, 13, and 14 are reported here for the first time. The main structural feature of these compounds is the reverse linkage of the two aromatic moieties, where the acid chloride moiety is linked to the phenolic group while preserving α,β-unsaturated ketone functionality. The cytotoxic screening of 7, 8, 9, and 10 at 50 and 10 μg/mL was carried out with human cancer cell lines K562, MCF-7, and SKLU-1. Lipid peroxidation on rat brain was also tested for compounds 7 and 10. Compounds 7, 8, and 10 showed relevant cytotoxic activity against these cancer cell lines, and 10 showed a protective effect against lipid peroxidation. The molecular resemblance to curcuminoids and analogs with ortho substituents suggests a potential source of useful bioactive compounds.
Synthesis and studies of the inhibitory effect of hydroxylated phenylpropanoids and biphenols derivatives on tyrosinase and laccase enzymes
Dettori, Maria Antonietta,Fabbri, Davide,Dessì, Alessandro,Dallocchio, Roberto,Carta, Paola,Honisch, Claudia,Ruzza, Paolo,Farina, Donatella,Migheli, Rossana,Serra, Pier Andrea,Pantaleoni, Roberto A.,Fois, Xenia,Rocchitta, Gaia,Delogu, Giovanna
, (2020)
The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccase inhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturally occurring compounds and their activity was measured by spectrophotometric and electrochemical assays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detect the type of protein-ligand interaction and half maximal inhibitory concentration (IC50). Most of the inhibitors showed an IC50 in a range of 20–423 nM for tyrosinase and 23–2619 nM for laccase. Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the new compounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 μM. In silico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing a prenylated chain as the lead structure, which activated strong and effective interactions at the active site of the enzyme. These data were confirmed by in vivo experiments performed on the insect model Tenebrio molitur.
Prenylated Curcumin Analogues as Multipotent Tools to Tackle Alzheimer's Disease
Bisceglia, Federica,Seghetti, Francesca,Serra, Massimo,Zusso, Morena,Gervasoni, Silvia,Verga, Laura,Vistoli, Giulio,Lanni, Cristina,Catanzaro, Michele,De Lorenzi, Ersilia,Belluti, Federica
, p. 1420 - 1433 (2019)
Alzheimer's disease is likely to be caused by copathogenic factors including aggregation of Aβ peptides into oligomers and fibrils, neuroinflammation, and oxidative stress. To date, no effective treatments are available, and because of the multifactorial nature of the disease, it emerges the need to act on different and simultaneous fronts. Despite the multiple biological activities ascribed to curcumin as neuroprotector, its poor bioavailability and toxicity limit the success in clinical outcomes. To tackle Alzheimer's disease on these aspects, the curcumin template was suitably modified and a small set of analogues was attained. In particular, derivative 1 turned out to be less toxic than curcumin. As evidenced by capillary electrophoresis and transmission electron microscopy studies, 1 proved to inhibit the formation of large toxic Aβ oligomers, by shifting the equilibrium toward smaller nontoxic assemblies and to limit the formation of insoluble fibrils. These findings were supported by molecular docking and steered molecular dynamics simulations which confirmed the superior capacity of 1 to bind Aβ structures of different complexity. Remarkably, 1 also showed in vitro anti-inflammatory and antioxidant properties. In summary, the curcumin-based analogue 1 emerged as multipotent compound worthy to be further investigated and exploited in the Alzheimer's disease multitarget context.
Synthesis of new ferrocenyl dehydrozingerone derivatives and their effects on viability of PC12 cells
Pedotti, Sonia,Patti, Angela,Dedola, Sonia,Barberis, Antonio,Fabbri, Davide,Dettori, Maria Antonietta,Serra, Pier Andrea,Delogu, Giovanna
, p. 80 - 89 (2016)
A series of novel compounds deriving from the conjugation of ferrocene with curcumin-related bioactive molecules as dehydrozingerone, zingerone and their biphenyl dimers was prepared by Claisen-Schmidt condensation of the suitable aromatic aldehydes and acetylferrocene in different conditions according to the starting material. The obtained compounds were fully characterized by NMR spectroscopy and cyclic voltammetry and reversible electrochemical behavior was recorded for monomer derivatives. The cell viability of PC12 cells after exposure to the organometallic compounds was also evaluated and a reduced toxicity with respect to the ferrocene was detected. In comparison with biphenyl 4, a compound that manifested antiproliferative and apoptotic activities and was quite toxic on PC12 cells, the exposure to the ferrocenyl analogue 14 resulted in roughly fourfold increase in the cell viability. Ferrocenyl chalcones 14 and 16-18 significantly increased the oxidative stress generated by hydrogen peroxide, a molecule generally accumulated in cancer cells and, recently, studied as prodrug.
Heterogeneous Catalytic Synthesis of Zingerone and Dehydrozingerone
Chistyakov, A. V.,Chistyakova, P. A.,Tsodikov, M. V.
, p. 1080 - 1086 (2020)
Abstract: Results of a single-stage heterogeneous catalytic synthesis of zingerone and dehydrozingerone have been described. The prospects of the proposed approach have been shown; the main kinetic laws governing the reaction have been revealed. Optimum conditions for zingerone and dehydrozingerone synthesis providing a yield of the target products of 45.8 and 76.2%, respectively, have been found.
Biocatalytic Properties and Structural Analysis of Eugenol Oxidase from Rhodococcus jostii RHA1: A Versatile Oxidative Biocatalyst
Nguyen, Quoc-Thai,de Gonzalo, Gonzalo,Binda, Claudia,Rioz-Martínez, Ana,Mattevi, Andrea,Fraaije, Marco W.
, p. 1359 - 1366 (2016)
Eugenol oxidase (EUGO) from Rhodococcus jostii RHA1 had previously been shown to convert only a limited set of phenolic compounds. In this study, we have explored the biocatalytic potential of this flavoprotein oxidase, resulting in a broadened substrate scope and a deeper insight into its structural properties. In addition to the oxidation of vanillyl alcohol and the hydroxylation of eugenol, EUGO can efficiently catalyze the dehydrogenation of various phenolic ketones and the selective oxidation of a racemic secondary alcohol—4-(1-hydroxyethyl)-2-methoxyphenol. EUGO was also found to perform the kinetic resolution of a racemic secondary alcohol. Crystal structures of the enzyme in complexes with isoeugenol, coniferyl alcohol, vanillin, and benzoate have been determined. The catalytic center is a remarkable solvent-inaccessible cavity on the si side of the flavin cofactor. Structural comparison with vanillyl alcohol oxidase from Penicillium simplicissimum highlights a few localized changes that correlate with the selectivity of EUGO for phenolic substrates bearing relatively small p-substituents while tolerating o-methoxy substituents.
Microwave induced rate enhancement in aldol condensation
Kad,Kaur, Kanwal Preet,Singh, Vasundhara,Singh, Jasvinder
, p. 2583 - 2586 (1999)
The rate of formation of aldol condensed products using microwave of various aromatic aldehydes and ketones in aqueous medium dramatically enhanced with respect to conventional methods in high yield (50-95.2%).
Stability of curcumin in different solvent and solution media: UV–visible and steady-state fluorescence spectral study
Mondal, Satyajit,Ghosh, Soumen,Moulik, Satya P.
, p. 212 - 218 (2016)
In aqueous solution, curcumin is photodegradable (light sensitive), it is also self-degradable in the dark. In basic medium, the second process is enhanced. The dark process has been studied in water and also in a number of protic and aprotic solvents, and aqueous solutions of ionic liquids, pluronics, reverse micelles and salt. The kinetics of the process followed the first order rate law; a comparative as well as individual assessment of which has been made. The kinetics of curcumin self-degradation has been found to be fairly dependent on salt (NaCl) concentration. Curcumin molecules in solution may remain in the enol or keto–enol form. From the visible spectral analysis, an estimate of the proportions of these forms in aqueous ethanol medium has been made. The temperature effect on the visible and fluorescence spectra of curcumin has been also studied. The steady state fluorescence anisotropy of the photoactive curcumin has been evaluated in different solvent and solution media. The reversibility of the steady state fluorescence anisotropy of curcumin on heating and cooling conditions has been examined. The results herein presented are new and ought to be useful as the study of physicochemistry of curcumin has been gaining importance in the light of its biological importance.
Synthesis and anticancer activity of chalcone analogues with sulfonyl groups
Mu?kinja, Jovana M.,Burmud?ija, Adrijana Z.,Baski?, Dejan D.,Popovi?, Suzana L.,Todorovi?, Danijela V.,Zari?, Milan M.,Ratkovi?, Zoran R.
, p. 279 - 291 (2019)
Three series of sulfonyl esters were synthesized in reactions of sulfonyl chlorides with three different phenolic chalcone analogues (dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one), (E)-1-(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one, and (E)-1-(4-hydroxy-3-methoxyphenyl)-5-methylhex-1-en-3-one). The structures of the new compounds were determined by IR, MS, and NMR methods. Screening of the new sulfonyl esters’ in vitro cytotoxic activities against human epithelial cervical carcinoma (HeLa) and normal human fibroblast (MRC-5) cell lines by the MTT method was performed. The five most active were selected and further tested on HeLa, MRC-5, and MCF-7 (breast carcinoma) cell lines. The examined compounds exhibit strong in vitro anticancer activities with moderate-to-high selectivity, inducing apoptotic cell death and cell cycle arrest in both HeLa and MCF-7 cell lines, but have little to no effect on the non-cancerous MRC-5 cell line.
A simple and efficient method for selective single aldol condensation between arylaldehydes and acetone
Paul, Satya,Gupta, Monika
, p. 213 - 222 (2005)
A simple and efficient method has been developed for selective single aldol condensation between acetone and various aromatic/heterocyclic aldehydes using aqueous sodium hydroxide at 5-10°C.
Structure and synthesis of [n]-dehydroshogaols from Zingiber officinale
Wu, Tian-Shung,Wu, You-Cheng,Wu, Pei-Lin,Chern, Ching-Yuh,Leu, Yann-Lii,Chan, Yu-Yi
, p. 889 - 891 (1998)
Three new dehydroshogaols have been isolated from the rhizomes of Zingiber officinale. Their structures were established by spectroscopic analysis and synthesis.
Insect growth inhibition, antifeedant and antifungal activity of compounds isolated/ derived from Zingiber officinale Roscoe (ginger) rhizomes
Agarwal, Manjree,Walia, Suresh,Dhingra, Swaran,Khambay, Bhupinder P. S.
, p. 289 - 300 (2001)
Fresh rhizomes of Zingiber officinale (ginger), when subjected to steam distillation, yielded ginger oil in which curcumene was found to be the major constituent. The thermally labile zingiberene-rich fraction was obtained from its diethyl ether extract. Column chromatography of ginger oleoresin furnished a fraction from which [6]-gingerol was obtained by preparative TLC. Naturally occurring [6]-dehydroshogaol was synthesised following condensation of dehydrozingerone with hexanal, whereas zingerone and 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)butane were obtained by hydrogenation of dehydrozingerone with 10% Pd/C. The structures of the compounds were established by 1H NMR, 13C NMR and mass (EI-MS and ES-MS) spectral analysis. The test compounds exhibited moderate insect growth regulatory (IGR) and antifeedant activity against Spilosoma obliqua, and significant antifungal activity against Rhizoctonia solani. Among the various compounds, [6]-dehydroshogaol exhibited maximum IGR activity (EC50 3.55mg ml-1) while dehydrozingerone imparted maximum antifungal activity (EC50 86.49mg litre-1).
Dehydrozingerone, a structural analogue of curcumin, induces cell-cycle arrest at the G2/M phase and accumulates intracellular ROS in HT-29 human colon cancer cells
Yogosawa, Shingo,Yamada, Yasumasa,Yasuda, Shusuke,Sun, Qi,Takizawa, Kaori,Sakai, Toshiyuki
, p. 2088 - 2093 (2012)
Dehydrozingerone (1) is a pungent constituent present in the rhizomes of ginger (Zingiber officinale) and belongs structurally to the vanillyl ketone class. It is a representative of half the chemical structure of curcumin (2), which is an antioxidative yellow pigment obtained from the rhizomes of turmeric (Curcuma longa). Numerous studies have suggested that 2 is a promising phytochemical for the inhibition of malignant tumors, including colon cancer. On the other hand, there have been few studies on the potential antineoplastic properties of 1, and its mode of action based on a molecular mechanism is little known. Therefore, the antiproliferative effects of 1 were evaluated against HT-29 human colon cancer cells, and it was found that 1 dose-dependently inhibited growth at the G2/M phase with up-regulation of p21. Dehydrozingerone additionally led to the accumulation of intracellular ROS, although most radical scavengers could not clearly repress the cell-cycle arrest at the G2/M phase. Furthermore, two synthetic isomers of 1 (iso-dehydrozingerone, 3, and ortho-dehydrozingerone, 4) were also examined. On comparing of their activities, accumulation of intracellular ROS was found to be interrelated with growth-inhibitory effects. These results suggest that analogues of 1 may be potential chemotherapeutic agents for colon cancer.
A Thorough Study on the Photoisomerization of Ferulic Acid Derivatives
Moni, Lisa,Banfi, Luca,Basso, Andrea,Mori, Alessia,Risso, Federica,Riva, Renata,Lambruschini, Chiara
, p. 1737 - 1749 (2021/03/23)
A thorough study on the (E) to (Z) photoisomerization of ferulic acid derivatives (esters, amides of all types, and ketones) was carried out. At the photostationary state, only aliphatic or benzylic tertiary amides reach a nearly complete conversion of (E) isomers into the (Z) ones, whereas for esters, primary and secondary amides or aromatic tertiary amides mixtures of (Z)/(E) ranging from 7 : 93 to 72 : 28 are observed. Ketones show rather limited photoisomerization. However, (Z) ketones may be obtained by the reaction of organometal compounds with an isomerized (Z) Weinreb amide.
Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs
He, Wenfei,Wang, Jingsong,Jin, Qiling,Zhang, Jiafeng,Liu, Yugang,Jin, Zewu,Wang, Hua,Hu, Linya,Zhu, Lu,Shen, Mengya,Huang, Lili,Huang, Shengwei,Li, Wulan,Zhuge, Qichuan,Wu, Jianzhang
, (2021/07/06)
Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure–activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.
