co9b00186_si_001.pdf (6.8 MB)
Diversity-Oriented Library Synthesis from Steviol and Isosteviol-Derived Scaffolds
journal contribution
posted on 2020-02-17, 19:33 authored by Trinh
A. D. Holth, Michael A. Walters, Oliver E. Hutt, Gunda I. GeorgThe readily available natural product
stevioside provides a unique diterpene core structure that can be
explored for small molecule library development by diversity-oriented
synthesis and functional group transformations. Validation arrays
were prepared from steviol, isosteviol, and related analogues, derived
from stevioside, to produce over 90 compounds. These compounds were
submitted to the NIH Molecular Libraries Small Molecule Repository
for screening in the Molecular Libraries Screening Center Network.
Micromolar hits were identified in multiple high-throughput assays
for several library members. A cheminformatics analysis of the compounds
was performed that verified the expected diversity and complexity
of this set of compounds. The screening results indicate that scaffolds-derived
natural products can provide screening hits against multiple target
proteins.
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cheminformatics analysisMolecular Libraries Screening Center Networkgroup transformationsdiversity-oriented synthesisditerpene core structurescreening hitsMolecule Repositoryscreening resultsMicromolar hitsNIH Molecular Librariesmolecule library developmentValidation arrayslibrary membersIsosteviol-Derived Scaffolds90 compoundsDiversity-Oriented Library Synthesisproduct steviosidetarget proteinshigh-throughput assays
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