Acid dissociation constant, a potential physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES)

• Published in: Bioorganic & medicinal chemistry letters 2001-04, Vol.11 (7), p.899-902
• Main Authors: Ahmed, Sabbir, Owen, Caroline P, James, Karen, Patel, Chirag K, Patel, Mijal
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Estrogens - metabolism; Estrone - analogs & derivatives; Estrone - metabolism; Estrone - pharmacology; General aspects; Inhibitory Concentration 50; Kinetics; Medical sciences; Pharmacology. Drug treatments; Phenols - chemical synthesis; Phenols - metabolism; Phenols - pharmacology; Structure-Activity Relationship; Sulfatases - antagonists & inhibitors; Sulfatases - metabolism; Sulfonic Acids - chemical synthesis; Sulfonic Acids - metabolism; Sulfonic Acids - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00087-7

We report the initial results of the synthesis and biochemical evaluation of a series of aminosulfonate based compounds of phenol and the determination of the p K a of the parent phenol in an attempt to investigate the role of this physicochemical factor in the irreversible inhibition of the enzyme estrone sulfatase (ES). The results of the study show that there is a strong correlation between the observed p K a and inhibitory activity. We postulate that the stability of the phenoxide ion, as indicated by the acid dissociation constant, is an important factor in the irreversible inhibition of this enzyme. A number of derivatives of phenyl sulfamate have been synthesized and their inhibitory activity considered against the p K a value of the starting phenol.