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Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.

ABSTRACT: Reported here are novel formic-acid-mediated rearrangements of dearomatized acylphloroglucinols to access a structurally diverse group of synthetic acylphloroglucinol scaffolds (SASs). Density-functional theory (DFT) optimized orbital and stereochemical analyses shed light on the mechanism of these rearrangements. Products were evaluated by multiplexed activity profiling (MAP), an unbiased platform which assays multiple biological readouts simultaneously at single-cell resolution for markers of cell signaling, and can aid in distinguishing genuine activity from assay interference. MAP identified a number of SASs that suppressed pS6 (Ser235/236), a marker for activation of the mTOR and ERK signaling pathways. These results illustrate how biomimetic synthesis and multiplexed activity profiling can reveal the pharmacological potential of novel chemotypes by diversity-oriented synthesis.

SUBMITTER: Boyce JH

PROVIDER: S-EPMC7855714 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.

Boyce Jonathan H JH Reisman Benjamin J BJ Bachmann Brian O BO Porco John A JA

Angewandte Chemie (International ed. in English) 20201130 3

Reported here are novel formic-acid-mediated rearrangements of dearomatized acylphloroglucinols to access a structurally diverse group of synthetic acylphloroglucinol scaffolds (SASs). Density-functional theory (DFT) optimized orbital and stereochemical analyses shed light on the mechanism of these rearrangements. Products were evaluated by multiplexed activity profiling (MAP), an unbiased platform which assays multiple biological readouts simultaneously at single-cell resolution for markers of ...[more]

PMID: 32965753

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Dataset Information

Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.

Publications

Synthesis and Multiplexed Activity Profiling of Synthetic Acylphloroglucinol Scaffolds.

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