Owen, C., James, K., Sampson, L. and Ahmed, S. (2003) Synthesis and biochemical evaluation of some novel benzoic acid based esters as potential inhibitors of oestrone sulphatase. Journal of Pharmacy and Pharmacology, 55(1), pp. 85-93. ISSN (print) 0022-3573Full text not available from this archive.
Oestrone sulphatase is an important target in the fight against hormone-dependent breast cancer. In an effort to investigate the reported definitive pharmacophore for oestrone sulphatase and continue our search for potent inhibitors of this enzyme, we have undertaken extensive synthesis, biochemical evaluation and physicochemical property determination of a range of benzoic acid based esters. Here, we report the initial results of our study into a series of straight chain alkyl esters of 4-sulphonylbenzoic acid. Using these compounds, we have investigated the involvement of two physicochemical properties, namely logP and pK(a). The results of this study show that there was a strong correlation between the inhibitory activity and the logP of the parent compound. Within the series of compounds studied, hydrophobicity appears to be a more important factor than pK(a) in determining the overall inhibitory activity. In a previous report, we showed that pK(a) plays an important role in stabilizing the phenoxide ion resulting from the hydrolysis of the sulphamate group. Here, we propose that although pK(a) is an important factor in determining the overall inhibitory activity when a wide range of compounds are considered, both hydrophobicity and pK(a) need to be considered in the design of potential inhibitors of oestrone sulphatase.
|Uncontrolled Keywords:||site-directed inhibition, estrone sulfatase, steroid sulfatase, aromatase inhibitors|
|Faculty, School or Research Centre:||Faculty of Science (until 2011) > School of Pharmacy and Chemistry|
|Depositing User:||Automatic Import Agent|
|Date Deposited:||10 Mar 2010 14:13|
|Last Modified:||02 Dec 2011 16:34|
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