Abstract
Celecoxib is a COX-2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma. Glucocorticoids are used in the treatment of inflammatory bowel disease. A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects. The prodrug systems introduced here involve forming a nitro-substituted acylsulfonamide group in the case of celecoxib and a nitro-substituted 21-ester for the glucocorticoids. Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species. The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco-2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs.
Copyright © 2013 Elsevier Ltd. All rights reserved.
MeSH terms
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / therapeutic use
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Antineoplastic Agents / toxicity
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Budesonide / chemistry*
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Budesonide / therapeutic use
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Budesonide / toxicity
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Caco-2 Cells
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Celecoxib
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Cell Membrane Permeability / drug effects
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Clostridium perfringens / drug effects
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Colorectal Neoplasms / drug therapy
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / therapeutic use
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Cyclooxygenase 2 Inhibitors / toxicity
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Humans
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Lactones / chemistry
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Nitrobenzenes / chemistry*
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Nitroreductases / metabolism
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Prednisolone / chemistry*
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Prednisolone / therapeutic use
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Prednisolone / toxicity
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Prodrugs / chemistry*
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Prodrugs / therapeutic use
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Prodrugs / toxicity
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Pyrazoles / chemistry*
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Pyrazoles / therapeutic use
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Pyrazoles / toxicity
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Sulfonamides / chemistry*
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Sulfonamides / therapeutic use
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Sulfonamides / toxicity
Substances
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Antineoplastic Agents
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Cyclooxygenase 2 Inhibitors
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Lactones
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Nitrobenzenes
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Prodrugs
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Pyrazoles
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Sulfonamides
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Budesonide
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Prednisolone
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nitrobenzene
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Nitroreductases
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Celecoxib