title: Design, synthesis and biochemical evaluation of AC ring mimics as novel inhibitors of the enzyme estrone sulfatase (ES).
abstract: We report the results of our study into a series of 4'-O-sulfamoyl-4-biphenyl based compounds as novel inhibitors of the enzyme estrone sulfatase (ES). From the results of the molecular modeling design process, it was suggested that these compounds would be able to mimic both the A and C rings of the steroid backbone, and thus possess inhibitory activity against ES. The results of the biochemical evaluation study show that these compounds are indeed good inhibitors, possessing greater inhibitory activity than COUMATE, but weaker inhibitory activity than EMATE or the tricyclic derivative of COUMATE, namely 667-COUMATE. Furthermore, the compounds are observed to be irreversible inhibitors.
authors.affiliation: School of Chemical and Pharmaceutical Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK. s.ahmed@kingston.ac.uk
authors.forename: Sabbir
authors.initials: S
authors.lastname: Ahmed
authors.forename: Karen
authors.initials: K
authors.lastname: James
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Owen
mesh_terms: D003374:Coumarins / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D013329:Structure-Activity Relationship; D013429:Sulfatases / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D013451:Sulfonic Acids
chemical_list: C100463:4-methylcoumarin 7-O-sulfamate; D003374:Coumarins; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D013451:Sulfonic Acids; C088768:estrone-3-O-sulfamate; D004970:Estrone; C520511:irosustat; D013429:Sulfatases; C020121:estrone sulfatase