1. A monocarbonyl curcuminoid derivative inhibits the activity of human glutathione transferase A4-4 and chemosensitizes glioblastoma cells to temozolomideSteliana Tsouri, Evanthia Tselo, Georgios E. Premetis, Veronika Furlan, Panagiota D. Pantiora, Barbara Mavroidi, Dimitris Matiadis, Maria Pelecanou, Anastassios C. Papageorgiou, Urban Bren, Marina Sagnou, Nikolaos E. Labrou, 2024, izvirni znanstveni članek Ključne besede: chemosensitization, chemoresistance, curcumin, glioblastoma, human glutathione transferase A4-4, ellagic acid, monocarbonyl curcumin derivatives, GST inhibition, temozolomide sensitization
Objavljeno v DKUM: 23.08.2024; Ogledov: 66; Prenosov: 9
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2. Monocarbonyl Curcumin Analogues as Potent Inhibitors against Human Glutathione Transferase P1-1Panagiota D. Pantiora, Veronika Furlan, Dimitris Matiadis, Barbara Mavroidi, Fereniki Perperopoulou, Anastassios C. Papageorgiou, Marina Sagnou, Urban Bren, Maria Pelecanou, Nikolaos E. Labrou, 2023, izvirni znanstveni članek Opis: The isoenzyme of human glutathione transferase P1-1 (hGSTP1-1) is involved in multi-drug resistance (MDR) mechanisms in numerous cancer cell lines. In the present study, the inhibition potency of two curcuminoids and eleven monocarbonyl curcumin analogues against hGSTP1-1 was investigated. Demethoxycurcumin (Curcumin II) and three of the monocarbonyl curcumin analogues exhibited the highest inhibitory activity towards hGSTP1-1 with IC50 values ranging between 5.45 1.08 and 37.72 1.02 M. Kinetic inhibition studies of the most potent inhibitors demonstrated that they function as non-competitive/mixed-type inhibitors. These compounds were also evaluated for their toxicity against the prostate cancer cells DU-145. Interestingly, the strongest hGSTP1-1 inhibitor, (DM96), exhibited the highest cytotoxicity with an IC50 of 8.60 1.07 M, while the IC50 values of the rest of the compounds ranged between 44.59–48.52 M. Structural analysis employing molecular docking, molecular dynamics (MD) simulations, and binding-free-energy calculations was performed to study the four most potent curcumin analogues as hGSTP1-1 inhibitors. According to the obtained computational results, DM96 exhibited the lowest binding free energy, which is in agreement with the experimental data. All studied curcumin analogues were found to form hydrophobic interactions with the residue Gln52, as well as hydrogen bonds with the nearby residues Gln65 and Asn67. Additional hydrophobic interactions with the residues Phe9 and Val36 as well as – stacking interaction with Phe9 contributed to the superior inhibitory activity of DM96. The van derWaals component through shape complementarity was found to play the most important role in DM96-inhibitory activity. Overall, our results revealed that the monocarbonyl curcumin derivative DM96 acts as a strong hGSTP1-1 inhibitor, exerts high prostate cancer cell cytotoxicity, and may, therefore, be exploited for the suppression and chemosensitization of cancer cells. This study provides new insights into the development of safe and effective GST-targeted cancer chemosensitizers.
Ključne besede: curcuminoids, curcumin analogues, human glutathione transferase P1-1 (hGSTP1-1), glutathione transferase, enzyme inhibition, multi-drug resistance
Objavljeno v DKUM: 12.03.2024; Ogledov: 288; Prenosov: 13
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3. The extraction process, separation, and identification of curcuminoids from turmeric curcuma longaGal Slaček, Petra Kotnik, Azra Osmić, Vesna Postružnik, Željko Knez, Matjaž Finšgar, Maša Knez Marevci, 2023, izvirni znanstveni članek Opis: Turmeric Curcuma longa is a well-known spice with various health benefits, attributed primarily to curcumin. Soxhlet extraction, cold maceration, ultrasound-assisted extraction (UAE), and supercritical fluid extraction were performed, and the content of total phenols, proanthocyanidins, and antioxidants was analysed by UV/VIS spectrophotometry. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed to identify and quantify the curcumin content. Supercritical extracts had the highest total phenolic content (538.95 mg GA/100 g material), while the Soxhlet extracts had the highest content of proanthocyanidins (4.77 mg PAC/100 g of material). Extracts obtained by UAE and supercritical extraction have the highest antioxidant potential. Antioxidant activity measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) was 64.27% and 1750.32 mg Trolox per g dry weight by 2,2-azinobis(3-ethylbenzothiazoline 6 sulphonic acid) (ABTS(+center dot)) for the extract obtained by supercritical extraction. The UAE resulted in the highest amount of curcumin (1.91 mg curcumin/g material). A kinetic study showed that extraction yield in supercritical extracts decreased with increasing temperature and that the content of isolated curcumin was inversely proportional to solvent-to-feed ratio (S/F). The present study has confirmed that turmeric is an excellent source of antioxidants, such as curcumin, that play an important role in reducing cellular stress by neutralising free radicals.
Ključne besede: turmeric, curcumin, total phenols, proanthocyanidins, antioxidants
Objavljeno v DKUM: 09.02.2024; Ogledov: 361; Prenosov: 50
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