Natural and natural-like polyphenol compounds: in vitro antioxidant activity and potential for therapeutic application

Introduction Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to preform an in vitro screening of natural and natural-like phenol monomers and their C2-symetric dimers (hydroxylated biphenyls) in order to identify those representatives which pharmacophores have the strongest antioxidant and the lowest prooxidant activity. Material and methods Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated in vitro. Different (red/ox) assays were used to measure their total oxidative potential (TOP), their total antioxidative capacity (TAC), the pro-oxidative-antioxidant balance (PAB) and total SH-group content (SHG) in a biologically relevant environment. The Pro-oxidative Score, Antioxidative Score and the Oxy Score were also calculated. Trolox, a water soluble analogue of αtocopherol was used as a positive control. Results In an assay consisting of pooled human serum 6 of the 36 compounds indicated significant antioxidant activity (compounds 6, 7, 12, 13, 26, and 27) whereas 4 indicated extremely weak antioxidant activity (compounds 2, 29, 30, and 31). Within the 36 compounds comprising of zingerone, dehydrozingerone, aurone, chalcone, magnolol derivatives, in both monomeric and dimeric forms, the 2 compounds that indicated the highest antioxidant activity were dehydrozingerone derivatives (compounds 6 and 12). Trolox’s activity was found between the strong and weak antioxidant compounds analysed in our study. Conclusions In this study selected dehydrozingerones were identified as good candidates for in-depth testing of their biological behaviour and for possible precursors for the synthesis of novel polyphenolic molecules with potential therapeutic applications. Powered by TCPDF (www.tcpdf.org) Pr ep rin t

[1]  Q. Migheli,et al.  Prenylated Trans-Cinnamic Esters and Ethers against Clinical Fusarium spp.: Repositioning of Natural Compounds in Antimicrobial Discovery , 2021, Molecules.

[2]  G. Delogu,et al.  Synthesis of Hydroxylated Biphenyl Derivatives Bearing an α,β‐Unsaturated Ketone as a Lead Structure for the Development of Drug Candidates against Malignant Melanoma , 2020, ChemMedChem.

[3]  G. Grześk,et al.  Resveratrol and cardiovascular system—the unfulfilled hopes , 2020, Irish Journal of Medical Science (1971 -).

[4]  M. Banach,et al.  Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study , 2020, Metabolites.

[5]  Maciej Banach,et al.  Potential effects of curcumin in the treatment of COVID‐19 infection , 2020, Phytotherapy research : PTR.

[6]  A. Simon,et al.  (±)-trans-Dihydronarciclasine and (±)-trans-dihydrolycoricidine analogues modified in their ring A: Evaluation of their anticancer activity and a SAR study. , 2019, European journal of medicinal chemistry.

[7]  M. Banach,et al.  Resveratrol and cognitive decline: a clinician perspective , 2019, Archives of medical science : AMS.

[8]  J. Simon,et al.  Phenolic-enriched raspberry fruit extract (Rubus idaeus) resulted in lower weight gain, increased ambulatory activity, and elevated hepatic lipoprotein lipase and heme oxygenase-1 expression in male mice fed a high-fat diet. , 2019, Nutrition research.

[9]  N. Mesbah,et al.  Raspberry ketone preserved cholinergic activity and antioxidant defense in obesity induced Alzheimer disease in rats. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  M. Cheng,et al.  Lipophilic antioxidants in neurodegenerative diseases. , 2018, Clinica chimica acta; international journal of clinical chemistry.

[11]  S. Yıldırım,et al.  Therapeutic efficacy of zingerone against vancomycin-induced oxidative stress, inflammation, apoptosis and aquaporin 1 permeability in rat kidney. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[12]  G. Durand,et al.  Nitrone-Trolox conjugate as an inhibitor of lipid oxidation: Towards synergistic antioxidant effects , 2018, bioRxiv.

[13]  M. Maioli,et al.  Synthesis of magnolol and honokiol derivatives and their effect against hepatocarcinoma cells , 2018, PloS one.

[14]  P. Glunz.  Recent encounters with atropisomerism in drug discovery. , 2018, Bioorganic & medicinal chemistry letters.

[15]  L. Saso,et al.  The Role of Oxidative Stress Modulators in Breast Cancer. , 2017, Current medicinal chemistry.

[16]  G. Lippi,et al.  Polyphenols: Potential Use in the Prevention and Treatment of Cardiovascular Diseases. , 2018, Current pharmaceutical design.

[17]  J. Bang,et al.  Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents. , 2017, Journal of medicinal chemistry.

[18]  D. Panagiotakos,et al.  Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel , 2017, Nutrition reviews.

[19]  A. Baschieri,et al.  Chain-breaking antioxidant activity of hydroxylated and methoxylated magnolol derivatives: the role of H-bonds. , 2017, Organic & biomolecular chemistry.

[20]  P. Ruzza,et al.  Hydroxylated biphenyls as tyrosinase inhibitor: A spectrophotometric and electrochemical study. , 2017, European journal of medicinal chemistry.

[21]  G. Delogu,et al.  The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation- and Oxidative Stress-Induced Dysfunction of In Vitro Cultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis , 2016, Oxidative medicine and cellular longevity.

[22]  M. Iranshahi,et al.  Prooxidant Activity of Polyphenols, Flavonoids, Anthocyanins and Carotenoids: Updated Review of Mechanisms and Catalyzing Metals , 2016, Phytotherapy research : PTR.

[23]  Yu-Ling Huang,et al.  Methylation and Esterification of Magnolol for Ameliorating Cutaneous Targeting and Therapeutic Index by Topical Application , 2016, Pharmaceutical Research.

[24]  V. V. Naumov,et al.  Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations , 2015, Beilstein journal of organic chemistry.

[25]  A. Stefanović,et al.  Oxidative stress and paraoxonase 1 status in acute ischemic stroke patients. , 2015, Atherosclerosis.

[26]  D. Pal,et al.  Free radicals, natural antioxidants, and their reaction mechanisms , 2015 .

[27]  A. Pappas.  Lipids and Skin Health , 2015, Springer International Publishing.

[28]  R. Amarowicz,et al.  Protective effects of equimolar mixtures of monomer and dimer of dehydrozingerone with α-tocopherol and/or ascorbyl palmitate during bulk lipid autoxidation. , 2014, Food chemistry.

[29]  J. Zhao,et al.  Dimer and Tetramer of Gallic Acid: Facile Synthesis, Antioxidant and Antiproliferative Activities , 2013 .

[30]  Lokender Kumar,et al.  Zingerone inhibit biofilm formation and improve antibiofilm efficacy of ciprofloxacin against Pseudomonas aeruginosa PAO1. , 2013, Fitoterapia.

[31]  L. Bubacco,et al.  Small molecules interacting with α-synuclein: antiaggregating and cytoprotective properties , 2013, Amino Acids.

[32]  D. Hadjipavlou-Litina,et al.  Recent progress in therapeutic applications of chalcones , 2011, Expert opinion on therapeutic patents.

[33]  Céline Douat-Casassus,et al.  Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis , 2011 .

[34]  N. Khalil.  Efficient synthesis of novel 1,2,4-triazole fused acyclic and 21-28 membered macrocyclic and/or lariat macrocyclic oxaazathia crown compounds with potential antimicrobial activity. , 2010, European journal of medicinal chemistry.

[35]  J. Jeong,et al.  Rheosmin, a naturally occurring phenolic compound inhibits LPS-induced iNOS and COX-2 expression in RAW264.7 cells by blocking NF-kappaB activation pathway. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[36]  J. Werba,et al.  Assessment of oxidative stress in coronary artery bypass surgery: comparison between the global index OXY-SCORE and individual biomarkers , 2009, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[37]  B. Bandgar,et al.  Antioxidant and anti-inflammatory related activities of selected synthetic chalcones: structure-activity relationship studies using computational tools. , 2008, Chemical & pharmaceutical bulletin.

[38]  M. Foti.  Antioxidant properties of phenols , 2007, The Journal of pharmacy and pharmacology.

[39]  G. Koliakos,et al.  A novel assay for the evaluation of the prooxidant-antioxidant balance, before and after antioxidant vitamin administration in type II diabetes patients. , 2007, Clinical biochemistry.

[40]  K. Lee,et al.  Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents. , 2006, Journal of natural products.

[41]  Chang Yong Lee,et al.  Sweet and sour cherry phenolics and their protective effects on neuronal cells. , 2005, Journal of agricultural and food chemistry.

[42]  O. Erel,et al.  A new automated colorimetric method for measuring total oxidant status. , 2005, Clinical biochemistry.

[43]  S. Danishefsky,et al.  En Route to the Total Synthesis of Tashironin: The Exercise of Stereochemical Control by a Methyl Group in Mediating Remote Cyclization Reactions. , 2005 .

[44]  V. Keshamouni,et al.  Curcumin for malaria therapy. , 2005, Biochemical and biophysical research communications.

[45]  Yeuk-Chuen Liu,et al.  Cytotoxic neolignans: an SAR study. , 2005, Bioorganic & medicinal chemistry letters.

[46]  Y. Murakami,et al.  Dimerization, ROS formation, and biological activity of o-methoxyphenols. , 2005, Archivum immunologiae et therapiae experimentalis.

[47]  O. Erel.  A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. , 2003, Clinical biochemistry.

[48]  M. Lucarini,et al.  Antioxidant activity of o-bisphenols: the role of intramolecular hydrogen bonding. , 2003, The Journal of organic chemistry.

[49]  W. Foye,et al.  Foye's Principles of Medicinal Chemistry , 2002 .

[50]  F. Visioli,et al.  The water-soluble vitamin E analogue Trolox protects against ischaemia/reperfusion damage in vitro and ex vivo. A comparison with vitamin E. , 2002, Pharmacological research.

[51]  P. Hajduk,et al.  Privileged molecules for protein binding identified from NMR-based screening. , 2000, Journal of medicinal chemistry.

[52]  Alfredo R. M. Oliveira,et al.  Oxidative coupling of 4-substituted 2-methoxy phenols using methyltributylammonium permanganate in dichloromethane , 1998 .

[53]  E. Decker.  Phenolics: prooxidants or antioxidants? , 2009, Nutrition reviews.

[54]  N. H. Tinh,et al.  Trioxatruxenes: A New Family of Disc-Like Mesogens with a Complex Polymorphism , 1984 .

[55]  J. Mašek.  [Nutrition and obesity]. , 1961, Vnitrni lekarstvi.

[56]  G. Ellman.  TISSUE SULPHYDRYL GROUPS , 1959 .