Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product-Inspired Library |
| |
| Authors: | Ryan S Hippman Ivan Pavlinov Qiwen Gao Michelle K Mavlyanova Erica M Gerlach Prof Leslie N Aldrich |
| |
| Affiliation: | 1. Department of Chemistry, University of Illinois at Chicago, 845?W. Taylor Street, Chicago, IL 60607 USA
These authors contributed equally to this work.;2. Department of Chemistry, University of Illinois at Chicago, 845?W. Taylor Street, Chicago, IL 60607 USA |
| |
| Abstract: | 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. |
| |
| Keywords: | biological performance diversity cell painting chemical diversity diversity-oriented synthesis flavonoid |
|
|
