ERA-ARE · A new ERA for Environmental Risk Assessment: Chirality as a tool towards environmentally safe pharmaceuticals

The detrimental effects on ecosystems and human health caused by the emerging contamination of aquatic environment by pharmaceuticals urges a disruptive prevention strategy. These drugs, their metabolites and transformation products (TPs) are stable, poorly biodegraded, and recalcitrant. Though novel mitigation measures have been proposed, they are insufficient and often risky due to the possible generation of TPs. Under this increasingly deteriorating scenario for future generations, ERA|ARE aspires to build a strong ground for the realization of an internationally leading research group dedicated to promoting environmental safety. ERA|ARE approach is based on fundamental understanding of enantioselectivity of environmental processes that can impact the fate/behaviour of pharmaceutical contaminants. Fluoroquinolones (FQs), a group of chiral fluorinated antibiotics/anti-cancer agents will be explored as a proof of concept, since most small molecules approved in the last years are either fluorinated and/or chiral, presenting a stable C–F bond and a potentially enantioselective bioactivity. To attain its goals, ERA|ARE will exploit the chirality of selected FQs as a piloting tool to: 1) realize the impact of stereochemistry on antimicrobial resistance (key innovation) by testing the hypothesis that antibiotic resistance (AR) may be acquired in (and not only spread/disseminated by) wastewater treatment plants (never verified before); 2) reveal how to better select drug candidates by biodegradability; 3) pave the way for future directions of Environmental Risk Assessment (ERA); and 4) avoid ecotoxicological effects and bioaccumulation. ERA|ARE will contribute to reduce AR (expected to cause 10 million deaths/year by 2050), raising the alert level for environmental protection and sustainability. ERA|ARE will rebrand the relationship pharmaceutical industry vs environment by disrupting the ERA process and creating pioneering guidelines for the pursuit of safer drugs.