Integration of Wnt-inhibitory activity and structural novelty scoring results to uncover novel bioactive natural products : new Bicyclo[3.3.1]non-3-ene-2,9-diones from the leaves of Hymenocardia punctata

Article Article scientifique Article Integration of Wnt-inhibitory activity and structural novelty scoring results to uncover novel bioactive natural products : new Bicyclo[3.3.1]non-3-ene-2,9-diones from the leaves of Hymenocardia punctata eng 2024-04-04 2024-04-04 author Quiros Guerrero Luis Manuel 0000-0002-1630-8697 902707 Section des sciences pharmaceutiques (FARMA) author Marcourt Laurence 729234 Section des sciences pharmaceutiques (FARMA) author Chaiwangrach Nathareen 991192 author Koval Alexey 0000-0002-8920-4426 910996 Département de physiologie cellulaire et métabolisme (PHYME) author Ferreira Queiroz Emerson 135675 Section des sciences pharmaceutiques (FARMA) author David Bruno author Grondin Antonio author Katanaev Vladimir 0000-0002-7909-5617 910192 Département de physiologie cellulaire et métabolisme (PHYME) author Wolfender Jean-Luc 135649 Section des sciences pharmaceutiques (FARMA) 1371982 10.3389/fchem.2024.1371982 2296-2646 https://www.frontiersin.org/articles/10.3389/fchem.2024.1371982/full In natural products (NPs) research, methods for the efficient prioritization of natural extracts (NEs) are key for discovering novel bioactive NPs. In this study a biodiverse collection of 1,600 NEs, previously analyzed by UHPLC-HRMS 2 metabolite profiling was screened for Wnt pathway regulation. The results of the biological screening drove the selection of a subset of 30 non-toxic NEs with an inhibitory IC 50 ≤ 5 μ g/mL. To increase the chance of finding structurally novel bioactive NPs, Inventa , a computational tool for automated scoring of NEs based on structural novelty was used to mine the HRMS 2 analysis and dereplication results. After this, four out of the 30 bioactive NEs were shortlisted by this approach. The most promising sample was the ethyl acetate extract of the leaves of Hymenocardia punctata (Phyllanthaceae). Further phytochemical investigations of this species resulted in the isolation of three known prenylated flavones ( 3 , 5 , 7 ) and ten novel bicyclo[3.3.1]non-3-ene-2,9-diones ( 1 , 2 , 4 , 6 , 8 – 13 ), named Hymenotamayonins . Assessment of the Wnt inhibitory activity of these compounds revealed that two prenylated flavones and three novel bicyclic compounds showed interesting activity without apparent cytotoxicity. This study highlights the potential of combining Inventa ’s structural novelty scores with biological screening results to effectively discover novel bioactive NPs in large NE collections. Dewey 612 Dewey 615 Swiss National Science Foundation An in silico and chemo-biological approach to identify anti-infective and pro-metabolic natural products 189921 CH Programmes 134 Département de physiologie cellulaire et métabolisme 21C 31 Section des sciences pharmaceutiques 17 false 1264 Voies de signalisation oncogéniques 998 882 Phytochimie et produits naturels bioactifs https://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=c9e133b094404c0ab373c991b8924fb0 https://massive.ucsd.edu/ProteoSAFe/dataset_files.jsp?task=ee8c8d92afd744c99ba0b6e1a53dfa0c#%7B%22table_sort_history%22%3A%22main.collection_asc%22%7D https://taxonomicallyinformedannotation.github.io/tima-r/index.html https://github.com/luigiquiros/inventa https://yareta.unige.ch/archives/1fcdd3ca-cd55-4f6f-b383-df1691c56411 Frontiers in chemistry 12 35d4e40c-c8ec-4152-9848-79414deb7e43 Article (Published version) Public Frontiers in Chemistry_2024.pdf 3049730 application/pdf CC BY-4.0 5d928fae4154c45cdcecdee42c79c8dd2dc4ce49abaafef17f24bcad8ae7caa1 85bfa67a-3814-4e4b-b268-df13b2f09053 Supplemental data Public Data Sheet 1-3.PDF 4447274 application/pdf 0f25a45d1e33517ee296ea300519842fba4cb0b9ac3f180d30cbdd60cbd1c9d7 openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté des sciences / Section des sciences pharmaceutiques

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Integration of Wnt-inhibitory activity and structural novelty scoring results to uncover novel bioactive natural products : new Bicyclo[3.3.1]non-3-ene-2,9-diones from the leaves of Hymenocardia punctata	Frontiers in chemistry			2024	129	118

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