Methoxy groups reduced the estrogenic activity of lignin-derivable replacements relative to bisphenol A and bisphenol F as studied through two in vitro assays

Abstract

Bisguaiacols are promising lignin-derivable alternatives to bisphenol A (BPA), but limited bioassay data are available on their estrogenic activity (EA). Herein, we investigated the estrogen receptor alpha (ERα)-mediated EA of six newly synthesized bisguaiacols, which differed in the number and location of methoxy substituents, through in vitro assays: MCF-7 cell proliferation and VM7Luc4E2 transactivation. The six bisguaiacols had undetectable EA at concentrations less than 10−7 M, most importantly, with significantly lower EA than BPA over an environmentally relevant range of 10−10–10−7 M. Adding a single methoxy group led to significant reduction in EA in all cases, relative to BPA and one petroleum-derived BPA analogue (bisphenol F, BPF), and the incorporation of more methoxy groups had subtler, but pronounced, impacts on either ERα binding or MCF-7 cell proliferation. In short, the six lignin-inspired bisguaiacols presented herein are viewed as promising sustainable alternatives to BPA and BPF.