Disconnecting the Estrogen Receptor Binding Properties and Antimicrobial Properties of Parabens through 3,5-Substitution.

Commercially utilized parabens are employed for their antimicrobial properties, but a weak binding to the estrogen receptor alpha (ERα ) may lead to breast cancer in some applications. Modification of the paraben scaffold should allow for a disconnection of these observed properties. Toward this goal, various 3,5-substituted parabens were synthesized and assessed for antimicrobial properties against S. aureus as well as competitive binding to the ERα . The minimum inhibitory concentration assay confirmed retention of antimicrobial activity in many of these derivatives, while all compounds exhibited decreased xenoestrogen activity as determined by a combination of competitive enzyme linked immunosorbent assay (ELISA), proliferation, and estrogen receptor binding assay. Thus, these changes to the paraben scaffold have led to a multitude of paraben derivatives with antimicrobial properties up to 16 times more active than the parent paraben and that are devoid or significantly diminished of potential breast cancer causing properties.