Antiviral Compounds from Codiaeum peltatum Targeted by a Multi-informative Molecular Networks Approach

Abstract

From a set of 292 Euphorbiaceae extracts, the use of a molecular networking (MN)-based prioritization approach highlighted three clusters (MN1−3) depicting ions from the bark extract of Codiaeum peltatum. Based on their putative antiviral potential and structural novelty, the MS-guided purification of compounds present in MN1 and MN2 afforded two new daphnane-type diterpenoid orthoesters (DDO), codiapeltines A (1) and B (2), the new actephilols B (3) and C (4), and four known 1,4-dioxane-fused phenanthrene dimers (5−8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis, and the absolute configurations of compounds 1 and 2 were deduced by comparison of experimental and calculated ECD spectra. Codiapeltine B (2) is the first daphnane bearing a 9,11,13-orthoester moiety, establishing a new major structural class of DDO. Compounds 1−8 and four recently reported monoterpenyl quinolones (9− 12) detected in MN3 were investigated for their selective activities against chikungunya virus replication and their antipolymerase activities against the NS5 proteins of dengue and zika viruses. Compounds 3−8 exhibited strong inhibitory activities on both dengue and zika NS5 in primary assays, but extensive biological analyses indicated that only actephilol B (3) displayed a specific interaction with the NS5 targets.

Characterization of Anti-Inflammatory and Antioxidant Constituents from Scutellaria baicalensis Using LC-MS Coupled with a Bioassay Method

“…Recently, molecular networking was introduced in drug development and metabolomics, particularly for natural products containing hundreds of components [8]. Molecular networking is mainly conjugated for prioritization specific structures that are expected to be active [2][3][4] and for annotation of bioactive extracts in natural products [5,9].…”

Innovative omics-based approaches for prioritisation and targeted isolation of natural products – new strategies for drug discovery

“…In this respect, an innovative LC-MS/MS-MN-based approach has been developed for the screening of a focused library of Euphorbiaceae plant species. 10,59,60 For this purpose, various layers of information such as biological results and/or taxonomic data have been used to discriminate specic ion clusters to allow for the in ne targeting the isolation of structurally new bioactive NPs. 10 Results of the biological screening of extracts using a chikungunya virus (CHIKV) cell-based assay and an oncogenic Wnt signalling assay were mapped to the MN, and colour tags were applied depending on the IC 50 or EC 50 values obtained.…”

“…From 1231 clusters containing $three nodes, 82 genus-specic ones were selected, among which one was sample-specic and resulted in the characterisation of ve unprecedented tetracyclic chlorinated monoterpenyl quinol-4one, two new daphnane diterpenoid orthoesters possessing potent anti-CHIK activities, and two new 1,4-dioxane-fused phenanthrene dimers, of which one was the rst natural dual inhibitor of dengue and Zika NS5 characterised to date. 60 When using such taxonomical layouts within a homogeneous set of samples, family-, genus-and species-specic compounds can be more easily distinguished from other ubiquitous NPs in an MN, signicantly increasing chances of discovering structurally new lead compounds. To further target bioactive NPs within complex mixtures, a bioactive MN work-ow integrating an algorithm that predicts putative bioactive molecules present in fractions has recently been added to GNPS methods.…”

Natural Products as a Foundation for Drug Discovery

“…Physicochemical data, in particular UV spectra and mass spectra, can rapidly limit the scope of possible compounds, especially when combined with analytical HPLC (Lang et al., ). Efforts to construct a large public database of mass spectral data are beginning to bear fruit (Allard et al., ; Covington, McLean, & Bachmann, ; Nothias et al., ; Olivon et al., , ; Wang et al., ). Although NMR database tools have also advanced, they are less comprehensive than the mass spectral findings (Bakiri et al., ; Buedenbender et al., ; Zhang et al., ).…”