A Meroisoprenoid, Heptenolides, and C-Benzylated Flavonoids from Sphaerocoryne gracilis ssp. gracilis.

Gasper Maeda,Jerry Pelletier,Vicky M Avery,Sandra Duffy,Stephen S Nyandoro,Sofia Lindblad,Joan J E Munissi,Máté Erdélyi

doi:10.1021/acs.jnatprod.9b00721

Abstract

A new meroisoprenoid (1), two heptenolides (2 and 3), two C-benzylated flavonoids (4 and 5), and 11 known compounds (6–16) were isolated from leaf, stem bark, and root bark extracts of Sphaerocoryne gracilis ssp. gracilis by chromatographic separation. The structures of the new metabolites 1–5 were established by NMR, IR, and UV spectroscopic and mass spectrometric data analysis. (Z)-Sphaerodiol (7), (Z)-acetylmelodorinol (8), 7-hydroxy-6-hydromelodienone (10), and dichamanetin (15) inhibited the proliferation of Plasmodium falciparum (3D7, Dd2) with IC50 values of 1.4–10.5 μM, although these compounds also showed cytotoxicity against human embryonic kidney HEK-293 cells. None of the compounds exhibited significant disruption in protein translation when assayed in vitro.

Highlights

The genus Sphaerocoryne (Annonaceae), formerly known as Melodorum, consists of the three species S. f ruticosum, S. gracilis, and S. punctulatum
Compound 1 was obtained as a colorless oil and was assigned the molecular formula C21H23O6 based on HRESIMS (Figure S9, Supporting Information) and NMR data (Table 1, Figures S2−S8, Supporting Information)
The above spectroscopic features are reminiscent of a butenolide system with an extension of an alicyclic three-carbon skeleton forming a heptenolide moiety, which has previously been reported for similar metabolites.4−7,10,11 Overall, the NMR data of 3 resembled that of (Z)-acetylmelodorinol [8] and of related compounds4−7,10,11 with the only difference being the ortho-hydroxy group substitution of its benzoyloxy group

Summary

■ RESULTS AND DISCUSSION

Repeated silica gel column chromatography of the methanolic extracts of the stem and root barks and leaves of Sphaerocoryne gracilis spp. gracilis, followed by gel filtration on Sephadex LH20 and further purification on HPLC, gave five new metabolites (1−5) and 11 known compounds (6−16, Figure S1, Supporting Information). The above spectroscopic features are reminiscent of a butenolide system with an extension of an alicyclic three-carbon skeleton forming a heptenolide moiety, which has previously been reported for similar metabolites.− Overall, the NMR data of 3 resembled that of (Z)-acetylmelodorinol [8] and of related compounds− with the only difference being the ortho-hydroxy group substitution of its benzoyloxy group The placement of this hydroxy group functionality was established by the ABCD coupling pattern of the aromatic signals (1H NMR, COSY, and TOCSY) and by HMBC correlations (Table 2, Figure S24, Supporting Information). Compound 4 was obtained as a white powder and was assigned the molecular formula C22H19O6, based on the HRESIMS (Figure S33, Supporting Information) and NMR (Table 4) data. Antiplasmodial activity was determined using a high-content imaging assay, as described previously. The cytotoxicity of the antiplasmodial compounds was evaluated against human embryonic kidney cells (HEK-293) following an established protocol. Human red blood cells for culture of P. falciparum were provided by the Australian Red

Cross Blood Bank in accordance with their routine Material Transfer

Corresponding Authors

■ ACKNOWLEDGMENTS

■ REFERENCES