An approach towards the quantitative structure-activity relationships for sulfamate-based estrone sulfatase inhibitors

Estrone sulfatase (ES) is a membrane-bound enzyme that is responsible for maintaining high levels of estrogens in breast cancer cells. This may be due to the conversion of estrone-sulfate into estrone by estrone-sulfatase, which acts as a pool of potentially available estrogens. There is now abundant evidence that estrogens have a pivotal role in the growth and development of hormone-dependent breast cancer. Thus, inhibitors of ES should have considerable therapeutic potential for the treatment of hormone-dependent breast cancer. Recently, a large number of sulfamate-based steroidal and non-steroidal ES inhibitors have been developed. The sulfamate moiety is believed to be involved in the irreversible inhibition of ES. In the present paper, we have undertaken quantitative structure-activity relationships for different series of non-steroidal sulfamate-based compounds in order to understand the chemical-biological interactions governing their inhibitory potency against ES. QSAR results have shown that the inhibitory potency against ES for these nonsteroidal sulfamate-based compounds is largely dependent on their hydrophobicity and molar refractivity.