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

Bridget L Bergquist; Kaelyn G Jefferson; Hailey N Kintz; Amorette E Barber; Andrew A Yeagley

doi:10.1021/acsmedchemlett.7b00431

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

ACS Med Chem Lett. 2017 Dec 15;9(1):51-55. doi: 10.1021/acsmedchemlett.7b00431. eCollection 2018 Jan 11.

Authors

Bridget L Bergquist¹, Kaelyn G Jefferson¹, Hailey N Kintz¹, Amorette E Barber¹, Andrew A Yeagley¹

Affiliation

¹ Department of Chemistry and Physics, Longwood University, 201 High Street, Farmville, Virginia 23909, United States.

Abstract

Commercially utilized parabens are employed for their antimicrobial properties, but a weak binding to the estrogen receptor alpha (ER_α) 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 ER_α. 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.