Putting benign by design into practice-novel concepts for green and sustainable pharmacy: Designing green drug derivatives by non-targeted synthesis and screening for biodegradability

• Pharmaceuticals in the environment are an increasing concern.
• Development of biodegradable pharmaceuticals would be attractive.
• Drug variants could be derivatised by non-targeted syntheses.
• Variants could be selected for variants with improved degradability and pharmacology.
• In silico methods could be combined with experimental approaches.
• The field of sustainable pharmacy will need interdisciplinary efforts.

Pharmaceuticals in the environment are an increasing concern, since the improvement of analytical tools has enabled the detection of parent compounds, metabolites and transformation products of a wide range of pharmaceuticals. These micro-pollutants might compromise the water quality and therefore might become a risk for the environment in general and particularly for humans. Major concerns are for example antibiotics. Antibiotics are used to control infections with pathogenic bacteria. Excessive utilization of non-degradable antibiotics by human patients or in farm animals might lead to accumulation in the water compartment and subsequently to the promotion of resistance development when wide areas containing relevant bacteria have sufficient concentrations of active antibiotics leading to a constant selection pressure on the bacteria. Therefore, it would be attractive to develop a new generation of biodegradable antibiotics, which would rapidly disintegrate into innoxious and in the best case inorganic molecules such as water, carbonate, nitrate and alike in sewage treatment plants or surface water. The guiding principle is the “benign by design” concept.