In:
Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 10 ( 2023-6-6)
Abstract:
A pigment-depleted extract from the heartwood of Pterocarpus santalinus L. f. (PS-DE) showed promising anti-SARS-CoV-2 activity with an IC 50 of 29.9 μg/mL in Caco-2-F03 cells. To determine the potential active constituents within the extract prior to isolation, multi-informative molecular network (MN) was applied. Therefore, the extract was separated by high-performance counter-current chromatography (HPCCC) into 11 fractions which were subsequently tested for anti-SARS-CoV-2 activity and analysed by UPLC-tandem mass spectrometry (MS 2 ). The resulting MN combines the bioactivity data of the fractions with the MS 2 data. The MN analysis led to the targeted isolation of seven compounds including one pterocarpan (7) reported for the first time as constituent of P. santalinus and four so far undescribed natural products (NPs) that belong to the compound classes of arylpropanes (9) , isoflavanones (10) coumestans (16) and 3-arylcoumarins (17) , respectively. In total, 15 constituents from the heartwood of P. santalinus and one synthetic isoflavonoid that is structurally related to the natural metabolites were tested for anti-SARS-CoV-2 activity. Thereby, the two pterocarpans (−)-homopterocarpin (5) and (−)-medicarpin (2) , the stilbene (E) -pterostilbene (1) and the isoflavonoid 7-O-methylgenistein (11) showed a distinct antiviral activity with IC 50 values of 17.2, 33.4, 34.7, and 37.9 µM, respectively, and no cytotoxic effects against Caco-2-F03 cells (CC 50 & gt; 100 µM). In addition, a structure-activity relationship (SAR) was proposed indicating structural requirements of pterocarpans for anti-SARS-CoV-2 activity. The herein presented results support the implementation of multi-informative molecular networks as powerful tool for dereplication and targeted isolation of bioactive NPs.
Type of Medium:
Online Resource
ISSN:
2296-889X
DOI:
10.3389/fmolb.2023.1202394
DOI:
10.3389/fmolb.2023.1202394.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2814330-9
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