Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products.

Angewandte Chemie
Jie LiuHerbert Waldmann

Abstract

Natural product (NP) structures are a rich source of inspiration for the discovery of new biologically relevant chemical matter. In natural product inspired pseudo-NPs, NP-derived fragments are combined de novo in unprecedented arrangements. Described here is the design and synthesis of a 155-member pyrroquinoline pseudo-NP collection in which fragments characteristic of the tetrahydroquinoline and pyrrolidine NP classes are combined with eight different connectivities and regioisomeric arrangements. Cheminformatic analysis and biological evaluation of the compound collection by means of phenotyping in the morphological "cell painting" assay followed by principal component analysis revealed that the pseudo-NP classes are chemically diverse and that bioactivity patterns differ markedly, and are dependent on connectivity and regioisomeric arrangement of the fragments.

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Citations

Mar 2, 2021·Angewandte Chemie·George KarageorgisHerbert Waldmann
May 12, 2021·Angewandte Chemie·Lucia FuriassiPaul J Hergenrother
Sep 14, 2021·Chemistry of Heterocyclic Compounds·Vladislav Yu ShuvalovAlexander S Fisyuk
Oct 21, 2021·Journal of Chemical Information and Modeling·José-Manuel GallyHerbert Waldmann

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