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

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 (ER alpha)-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 ER alpha 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.

Automated summary

This study investigated the estrogenic activity of six newly synthesized bisguaiacols, which showed undetectable activity at concentrations lower than 10(-7) M and significantly lower activity than BPA within an environmentally relevant range. Addition of a single methoxy group led to a significant reduction in activity, while incorporation of more methoxy groups had subtle but pronounced impacts. In conclusion, these lignin-inspired bisguaiacols are seen as promising sustainable alternatives to BPA and BPF.