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Physicochemical and biopharmaceutical characterization of novel derivatives of gallic acid
Alhyari, Dania H.
Alhyari, Dania H.
Publication Date
2022
End of Embargo
Keywords
Gallic acid (GA), 3,45-Trimethoxybenzensulfonamide (TMBS), 3,4,5-Trihydroxybenzensulfonamide (THBS), Reactive oxygen species (ROS), Cytochrome P450 2D6 (CYP2D6), Parallel artificial membrane permeability (PAMPA), Human intestinal epithelial cells (HIEC-6), Oral bioavailability, Anti-inflammatory properties, Antioxidant
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
School of Pharmacy and Medical Sciences. Faculty of Life Sciences
Awarded
2022
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Abstract
Gallic acid is a known antioxidant and has anti-inflammatory activity in addition to other biological activities, but GA efficiency is restricted due to low permeability and low oral bioavailability. This study was designed to investigate the solubility, permeability, oral bioavailability, enzymatic stability with cytochrome CYP2D6, antioxidant and anti-inflammatory activity of novel gallic acid sulfonamide derivatives; TMBS, and THBS. In addition, a novel in silico permeability model was designed to predict the permeability and bioavailability of eighty derivatives of GA.
In sillico prediction of intestinal permeability of GA derivative indicated an increase in permeability with increased lipophilicity and decreased aqueous solubility, replacing the carboxylic group with sulfonamide group has increased intestinal permeability. A significant (P <0.01) increase was observed in the permeability of TMBS and THBS over GA, in both gastric fluids and HIEC cells. TMBS was O-demethylated by CYP2D6. TMBS had greater ROS scavenging activity than GA in HIEC-6 cells. There was a significant (P< 0.05) increase in anti-inflammatory activity of THBS, and TMBS compared to ibuprofen. TMBS, and THBS had better oral bioavailability than GA.
This data suggests that the in silico permeability model can be used in the future to study new candidate of gallic acid, and further in vivo and clinical investigations are required to introduce TMBS and THBS as a new antioxidant and anti-inflammatory drugs.
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Type
Thesis
Qualification name
PhD