title: Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1.
abstract: Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of 17β-estradiol (17β-E2) from the 3- to the 17-position. The effects of celecoxib on the sulfonation of selected steroids catalyzed by human SULT2A1 were assessed through in vitro and in silico studies. Celecoxib inhibited SULT2A1-catalyzed sulfonation of dehydroepiandrosterone (DHEA), androst-5-ene-3β, 17β-diol (AD), testosterone (T) and epitestosterone (Epi-T) in a concentration-dependent manner. Low μM concentrations of celecoxib strikingly enhanced the formation of the 17-sulfates of 6-dehydroestradiol (6D-E2), 17β-dihydroequilenin (17β-Eqn), 17β-dihydroequilin (17β-Eq), and 9-dehydroestradiol (9D-E2) as well as the overall rate of sulfonation. For 6D-E2, 9D-E2 and 17β-Eqn, celecoxib inhibited 3-sulfonation, however 3-sulfonation of 17β-Eq was stimulated at celecoxib concentrations below 40 μM. Ligand docking studies in silico suggest that celecoxib binds in the substrate-binding site of SULT2A1 in a manner that prohibits the usual binding of substrates but facilitates, for appropriately shaped substrates, a binding mode that favors 17-sulfonation.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610-0485, USA.
authors.forename: Sriram
authors.initials: S
authors.lastname: Ambadapadi
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610-0485, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Wang
authors.affiliation: Biomedical Mass Spectrometry Laboratory, Clinical Research Center, University of Florida, Gainesville, FL 32610-0322, USA.
authors.forename: Sergiu P
authors.initials: SP
authors.lastname: Palii
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610-0485, USA. Electronic address: mojames@ufl.edu.
authors.forename: Margaret O
authors.initials: MO
authors.lastname: James
mesh_terms: D015114:Androstenediol / Q000378:metabolism; D001665:Binding Sites; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004845:Epitestosterone / Q000378:metabolism; D004857:Equilin / Q000031:analogs & derivatives / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011994:Recombinant Proteins; D013449:Sulfonamides; D004857:Equilin; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004845:Epitestosterone; D004958:Estradiol; C014482:dihydroequilin; D015114:Androstenediol; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D000068579:Celecoxib
keywords: Celecoxib; Dehydroepiandrosterone; Estradiol; SULT2A1; Steroids; Sulfotransferase