Sphenostylisins A–K: Bioactive Modified Isoflavonoid Constituents of the Root Bark of Sphenostylis marginata ssp. erecta

Abstract

Sphenostylisins A–C (1–3), three complex dimeric compounds representing two novel carbon skeletons, along with an additional eight new compounds, sphenostylisins D–K (4–11), were isolated from the active chloroform-soluble extract of the root bark of S. marginata ssp. erecta using a bioactivity-guided isolation approach. The structures were elucidated by means of detailed spectroscopic analysis, including NMR and HRESIMS analysis, with tandem MS fragmentation utilized to further support the structures of 1–3. The absolute configuration of sphenostylisin C (3) was established by electronic circular dichroism analysis. Plausible biogenetic relationships between the modified isoflavonoids 1–11 are proposed, with a cyclization reaction of 9 conducted to support one of the biogenetic proposals made. All these pure isolates were evaluated against a panel of in vitro bioassays, and, among the results obtained, sphenostylisin A (1) was found to be a very potent NF-κB inhibitor (IC50 6 nM).

Discovery of Anticancer Agents of Diverse Natural Origin

“…The most interesting of the new compounds biologically, sphenostylisin A ( 4 ), exhibited IC 50 values, in turn, of 6 nM in a NFκB (p65) inhibition enzyme-linked immunosorbent assay (ELISA) and 1.6 μM against HT-29 human colon cancer cells. Sphenostylin A is complex dimeric compound for which the structure elucidation process required a detailed spectroscopic data analysis (78). …”

3-Phenylcoumarins as a Privileged Scaffold in Medicinal Chemistry: The Landmarks of the Past Decade

“…Compound 53 exhibited an excellent ERα antagonistic activity (IC 50 = 12 nM) and antiproliferative potency against MCF-7 cells, similar to tamoxifen [132]. The sphenostylisin A (Figure 2) has been found to be a very potent NF-κB inhibitor (IC 50 = 6 nM) with promising interest in cancer and inflammation [4].…”

“…It is worth highlighting that this compound is a potent NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) inhibitor, displaying different physiological functions. This compound is also overexpressed in some cancer cells [4]. 2 ,4 -Dinitro-3-phenylcoumarin was isolated from Rhizophora mucronata [5].…”

“…Sphenostylis marginata [4] Rhizophora mucronata [5] Selaginella rolandi-principis [6] Figure 2. Chemical structures of glycycoumarin and licoarylcoumarin.…”

Natural source, bioactivity and synthesis of 3-Arylcoumarin derivatives

“…Natural products containing 3-arylcoumarin compounds are mainly extracted and isolated from Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. and Glycyrrhiza inflata Bat. (Licorice) 35–38 , Mucuna birdwoodiana (Leguminosae) 39 , Sphenostylis marginata ssp (Fabaceae) 40 and Pongamiopsis pervilleana (Baill) 41 ( Table 1 ).…”