Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates
Objectives Many natural antioxidants have poor pharmacokinetic properties that impair their therapeutic use. For hydroxycinnamic acids (HCAs) and other phenolic antioxidants, their major drawback is their low lipophilicity and a rapid metabolism. The difluoromethyl group may be considered as a '...
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todo:paper_00223573_v68_n2_p233_Martinez2023-10-03T14:31:58Z Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates Martínez, M.D. Luna, L. Tesio, A.Y. Feresin, G.E. Durán, F.J. Burton, G. antioxidant activity bioisosteres difluoromethyl group hydroxycinnamic acids lipid peroxidation 1,1 diphenyl 2 picrylhydrazyl antioxidant beta carotene caffeic acid methyl 3 [3 acetyloxy 4 [(difluoromethyl)phenyl]]propenoate methyl 3 [4 acetyloxy [3 (difluoromethyl)phenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 hydroxyphenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 methoxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 hydroxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 methoxyphenyl]]propenoate unclassified drug 1,1-diphenyl-2-picrylhydrazyl antioxidant biphenyl derivative coumaric acid ferricyanide fluorinated hydrocarbon free radical picric acid antioxidant activity Article bleaching cell assay controlled study cyclic potentiometry differential pulse voltammetry drug structure electrochemical analysis erythrocyte fluorescence recovery after photobleaching human human cell hydrogen bond lipid peroxidation lipophilicity oxidation reduction potential cell culture chemical structure chemistry drug effects electrochemistry metabolism oxidation reduction reaction synthesis Antioxidants beta Carotene Biphenyl Compounds Cells, Cultured Coumaric Acids Electrochemistry Erythrocytes Ferricyanides Free Radicals Humans Hydrocarbons, Fluorinated Lipid Peroxidation Molecular Structure Oxidation-Reduction Picrates Objectives Many natural antioxidants have poor pharmacokinetic properties that impair their therapeutic use. For hydroxycinnamic acids (HCAs) and other phenolic antioxidants, their major drawback is their low lipophilicity and a rapid metabolism. The difluoromethyl group may be considered as a 'lipophilic hydroxyl' due to its hydrogen bond donor and acceptor properties; this prompted us to assess it as a bioisosteric replacement of a phenolic hydroxyl for increasing the lipophilicity of HCAs. Methods Six difluoromethyl-substituted methyl cinnamates (4a-c, 5a-c) related to caffeic acid were synthesized and their antioxidant activity evaluated by chemical (FRAP, DPPH scavenging, inhibition of β-carotene bleaching, at 1-200 μm), electrochemical (differential pulse voltammetry, cyclic voltammetry) and cell-based (inhibition of lipid peroxidation in erythrocytes, at 1 and 50 μm) assays. Key fndings Analogues 4a-c and 5a-c were inactive in FRAP and DPPH assays and only those containing a free phenolic hydroxyl (4a and 5a) exhibited electrochemical activity although with high redox potentials. Compounds 4a,b and 5a,b were active in the inhibition of β-carotene bleaching assay and all analogues inhibited lipid peroxidation in the human erythrocytes assay. Conclusions Lipophilic difluoromethyl-substituted cinnamic esters retain radical scavenging capabilities that prove useful to confer antioxidant properties in a non-polar environment. © 2016 Royal Pharmaceutical Society. Fil:Durán, F.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00223573_v68_n2_p233_Martinez |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
antioxidant activity bioisosteres difluoromethyl group hydroxycinnamic acids lipid peroxidation 1,1 diphenyl 2 picrylhydrazyl antioxidant beta carotene caffeic acid methyl 3 [3 acetyloxy 4 [(difluoromethyl)phenyl]]propenoate methyl 3 [4 acetyloxy [3 (difluoromethyl)phenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 hydroxyphenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 methoxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 hydroxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 methoxyphenyl]]propenoate unclassified drug 1,1-diphenyl-2-picrylhydrazyl antioxidant biphenyl derivative coumaric acid ferricyanide fluorinated hydrocarbon free radical picric acid antioxidant activity Article bleaching cell assay controlled study cyclic potentiometry differential pulse voltammetry drug structure electrochemical analysis erythrocyte fluorescence recovery after photobleaching human human cell hydrogen bond lipid peroxidation lipophilicity oxidation reduction potential cell culture chemical structure chemistry drug effects electrochemistry metabolism oxidation reduction reaction synthesis Antioxidants beta Carotene Biphenyl Compounds Cells, Cultured Coumaric Acids Electrochemistry Erythrocytes Ferricyanides Free Radicals Humans Hydrocarbons, Fluorinated Lipid Peroxidation Molecular Structure Oxidation-Reduction Picrates |
| spellingShingle |
antioxidant activity bioisosteres difluoromethyl group hydroxycinnamic acids lipid peroxidation 1,1 diphenyl 2 picrylhydrazyl antioxidant beta carotene caffeic acid methyl 3 [3 acetyloxy 4 [(difluoromethyl)phenyl]]propenoate methyl 3 [4 acetyloxy [3 (difluoromethyl)phenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 hydroxyphenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 methoxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 hydroxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 methoxyphenyl]]propenoate unclassified drug 1,1-diphenyl-2-picrylhydrazyl antioxidant biphenyl derivative coumaric acid ferricyanide fluorinated hydrocarbon free radical picric acid antioxidant activity Article bleaching cell assay controlled study cyclic potentiometry differential pulse voltammetry drug structure electrochemical analysis erythrocyte fluorescence recovery after photobleaching human human cell hydrogen bond lipid peroxidation lipophilicity oxidation reduction potential cell culture chemical structure chemistry drug effects electrochemistry metabolism oxidation reduction reaction synthesis Antioxidants beta Carotene Biphenyl Compounds Cells, Cultured Coumaric Acids Electrochemistry Erythrocytes Ferricyanides Free Radicals Humans Hydrocarbons, Fluorinated Lipid Peroxidation Molecular Structure Oxidation-Reduction Picrates Martínez, M.D. Luna, L. Tesio, A.Y. Feresin, G.E. Durán, F.J. Burton, G. Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| topic_facet |
antioxidant activity bioisosteres difluoromethyl group hydroxycinnamic acids lipid peroxidation 1,1 diphenyl 2 picrylhydrazyl antioxidant beta carotene caffeic acid methyl 3 [3 acetyloxy 4 [(difluoromethyl)phenyl]]propenoate methyl 3 [4 acetyloxy [3 (difluoromethyl)phenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 hydroxyphenyl]]propenoate methyl 3 [[3 (difluoromethyl) 4 methoxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 hydroxyphenyl]]propenoate methyl 3 [[4 (difluoromethyl) 3 methoxyphenyl]]propenoate unclassified drug 1,1-diphenyl-2-picrylhydrazyl antioxidant biphenyl derivative coumaric acid ferricyanide fluorinated hydrocarbon free radical picric acid antioxidant activity Article bleaching cell assay controlled study cyclic potentiometry differential pulse voltammetry drug structure electrochemical analysis erythrocyte fluorescence recovery after photobleaching human human cell hydrogen bond lipid peroxidation lipophilicity oxidation reduction potential cell culture chemical structure chemistry drug effects electrochemistry metabolism oxidation reduction reaction synthesis Antioxidants beta Carotene Biphenyl Compounds Cells, Cultured Coumaric Acids Electrochemistry Erythrocytes Ferricyanides Free Radicals Humans Hydrocarbons, Fluorinated Lipid Peroxidation Molecular Structure Oxidation-Reduction Picrates |
| description |
Objectives Many natural antioxidants have poor pharmacokinetic properties that impair their therapeutic use. For hydroxycinnamic acids (HCAs) and other phenolic antioxidants, their major drawback is their low lipophilicity and a rapid metabolism. The difluoromethyl group may be considered as a 'lipophilic hydroxyl' due to its hydrogen bond donor and acceptor properties; this prompted us to assess it as a bioisosteric replacement of a phenolic hydroxyl for increasing the lipophilicity of HCAs. Methods Six difluoromethyl-substituted methyl cinnamates (4a-c, 5a-c) related to caffeic acid were synthesized and their antioxidant activity evaluated by chemical (FRAP, DPPH scavenging, inhibition of β-carotene bleaching, at 1-200 μm), electrochemical (differential pulse voltammetry, cyclic voltammetry) and cell-based (inhibition of lipid peroxidation in erythrocytes, at 1 and 50 μm) assays. Key fndings Analogues 4a-c and 5a-c were inactive in FRAP and DPPH assays and only those containing a free phenolic hydroxyl (4a and 5a) exhibited electrochemical activity although with high redox potentials. Compounds 4a,b and 5a,b were active in the inhibition of β-carotene bleaching assay and all analogues inhibited lipid peroxidation in the human erythrocytes assay. Conclusions Lipophilic difluoromethyl-substituted cinnamic esters retain radical scavenging capabilities that prove useful to confer antioxidant properties in a non-polar environment. © 2016 Royal Pharmaceutical Society. |
| format |
JOUR |
| author |
Martínez, M.D. Luna, L. Tesio, A.Y. Feresin, G.E. Durán, F.J. Burton, G. |
| author_facet |
Martínez, M.D. Luna, L. Tesio, A.Y. Feresin, G.E. Durán, F.J. Burton, G. |
| author_sort |
Martínez, M.D. |
| title |
Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| title_short |
Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| title_full |
Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| title_fullStr |
Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| title_full_unstemmed |
Antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| title_sort |
antioxidant properties in a non-polar environment of difluoromethyl bioisosteres of methyl hydroxycinnamates |
| url |
http://hdl.handle.net/20.500.12110/paper_00223573_v68_n2_p233_Martinez |
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