Affiliation:
1. Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands
Abstract
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 (CyreneTM), 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.
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
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