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Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product‐Inspired Library
Author(s) -
Hippman Ryan S.,
Pavlinov Ivan,
Gao Qiwen,
Mavlyanova Michelle K.,
Gerlach Erica M.,
Aldrich Leslie N.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000356
Subject(s) - natural product , chemical space , diversity (politics) , appendage , scaffold , chemical biology , biochemical engineering , drug discovery , combinatorial chemistry , computer science , chemistry , nanotechnology , biology , engineering , stereochemistry , materials science , ecology , biochemistry , database , sociology , anthropology
A systematic, diversity‐oriented synthesis approach was employed to access a natural product‐inspired flavonoid library with diverse chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated, and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. In addition, the diversity of chemical properties contributed to performance diversity, and the driving chemical property was dependent on the scaffold. These results highlight the importance of key chemical features that may inform the creation of small‐molecule, performance‐diverse libraries to improve the efficiency and success of high‐throughput screening campaigns.