Natural product fragment combination to performance-diverse pseudo-natural products
| العنوان: | Natural product fragment combination to performance-diverse pseudo-natural products |
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| المؤلفون: | Herbert Waldmann, Andrey P. Antonchick, Niklas Wild, Sonja Sievers, José-Manuel Gally, Carsten Strohmann, Axel Pahl, Yannik Mantel, Sarah Zinken, Michael Grigalunas, Daniel J. Foley, Rebecca Scheel, Annina Burhop |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Indoles, Science, Chemical libraries, General Physics and Astronomy, Computational biology, 010402 general chemistry, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Natural (archaeology), Article, Griseofulvin, Small Molecule Libraries, chemistry.chemical_compound, Fragment (logic), Drug Discovery, Chemical synthesis, Biological evaluation, Biological Products, Multidisciplinary, Natural product, Product design, Quinine, 010405 organic chemistry, Cheminformatics, General Chemistry, Quinidine, Chemical space, humanities, 0104 chemical sciences, chemistry, Morphinans, Chromones, Product (mathematics), Identification (biology) |
| الوصف: | Natural product structure and fragment-based compound development inspire pseudo-natural product design through different combinations of a given natural product fragment set to compound classes expected to be chemically and biologically diverse. We describe the synthetic combination of the fragment-sized natural products quinine, quinidine, sinomenine, and griseofulvin with chromanone or indole-containing fragments to provide a 244-member pseudo-natural product collection. Cheminformatic analyses reveal that the resulting eight pseudo-natural product classes are chemically diverse and share both drug- and natural product-like properties. Unbiased biological evaluation by cell painting demonstrates that bioactivity of pseudo-natural products, guiding natural products, and fragments differ and that combination of different fragments dominates establishment of unique bioactivity. Identification of phenotypic fragment dominance enables design of compound classes with correctly predicted bioactivity. The results demonstrate that fusion of natural product fragments in different combinations and arrangements can provide chemically and biologically diverse pseudo-natural product classes for wider exploration of biologically relevant chemical space. Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::956383e93ab0b9c316a0e7f4df8f0597 https://doaj.org/article/c324981d1dd847a2877255197701b2a3 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....956383e93ab0b9c316a0e7f4df8f0597 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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