Login / Signup

Green Drug Discovery: Novel Fragment Space from the Biomass-Derived Molecule Dihydrolevoglucosenone (Cyrene TM ).

Tom DekkerJaap W HarteveldGábor WágnerMax C M de VriesHans CustersAndrea C van de StolpeIwan J P de EschMaikel Wijtmans
Published in: Molecules (Basel, Switzerland) (2023)
Biomass-derived molecules can provide a basis for sustainable drug discovery. However, their full exploration is hampered by the dominance of millions of old-fashioned screening compounds in classical high-throughput screening (HTS) libraries frequently utilized. We propose a fragment-based drug discovery (FBDD) approach as an efficient method to navigate biomass-derived drug space. Here, we perform a proof-of-concept study with dihydrolevoglucosenone (Cyrene TM ), a pyrolysis product of cellulose. Diverse synthetic routes afforded a 100-membered fragment library with a diversity in functional groups appended. The library overall performs well in terms of novelty, physicochemical properties, aqueous solubility, stability, and three-dimensionality. Our study suggests that Cyrene-based fragments are a valuable green addition to the drug discovery toolbox. Our findings can help in paving the way for new hit drug candidates that are based on renewable resources.
Keyphrases
  • drug discovery
  • wastewater treatment
  • anaerobic digestion
  • ionic liquid