A number of suggestions to increase the chances that an API molecule will not be persistent have been put forward, including:
- Tagging molecules with an affinity marker to allow extraction onto solid supports in Effluent/Sewage Treatment Plants (ETP/STP).
- Tagging molecules with functionality known to be degraded by aerobic/anaerobic bacteria.
- Increasing the photosensitivity of molecules to natural sunlight; if the UV maxima is < 290 nm, direct photolysis would not be expected to occur (although indirect photolysis might).
However, none of the above solutions would be practical or desirable as design options in medicinal chemistry. Probably the most practical solutions would be:
- If possible, avoid molecules or fragments known to give rise to environmental problems like PBT.
- If possible, choose functional groups that are more likely to be biologically degraded.
- Use natural product or natural product-like scaffolds.
- Get an early idea of possible PBT issues through screening – in vivo or in vitro or using animal/human toxicology data to ‘read across’ to other species.