Studies on the Nonalkaloidal Secondary Metabolites of Hippeastrum vittatum (L'Her.) Herb. Bulbs

Abstract

Sixteen chemically varied metabolites were isolated from the bulbs of Hippeastrum vittatum (L'Her.) Herb., including eight flavonoids [3'-methyl isoliquiritigenin (2), 7-hydroxyflavan (8), 7-hydroxyflavanone (9), 7-hydroxyflavan-3-ol (10), 7-methoxy-3',4'-methylenedioxyflavan-3-ol (11), 7-hydroxy-3',4'-methylenedioxy flavan (12), 2',4'-dihydroxy-3'-methyl-3,4-methylenedioxychalcone (13), and isoliquiritigenin (14)], four acetophenones [2,6-dimethoxy-4-hydroxyacetophenone (3), 2,4-dihydroxyacetophenone (4), 2,4-dihydroxy-6-methoxy-3-methylacetophenone (6), and 2,4,6-trimethoxyacetophenone (7)], two alkaloids [lycorine (1) and narciprimine (15)], one phenol derivative [p-nitrophenol (5)], and one steroid [β-sitosterol 3-O-β-glucopyranoside (16)]. Their structures were elucidated by combining one- and two-dimensional NMR and ESI-MS techniques and by comparison with the reported literature data and some authentic samples. Except for lycorine (1), the isolated metabolites were obtained herein for the first time from Hippeastrum plants, among which compound 13 was identified as a new chalcone derivative. Additionally, the total phenolic and flavonoid contents of the total ethanol extract and different fractions of the bulbs were determined by the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively, whereas their antioxidant potential was compared using the phosphomolybdenum and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. Finally, the binding affinities of compounds 1-16 to some key target proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, main protease (M^pro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp), were screened and compared using molecular docking analysis. The possible chemotaxonomic significance of the identified metabolites was also discussed.

Figure 1

Chemical structures of the isolated compounds 1–16 from H. vittatum bulbs.

Figure 2

Significant HMBC correlations of compound 13.

Figure 3

Plausible biosynthetic pathways of the isolated metabolites from H. vittatum bulbs.

Figure 4

Ligand interactions of compound 16 and N3 docked into the active site of SARS-CoV-2 M^pro ((A, B) 2D poses of compound 16 and N3; (C, D) 3D poses of compound 16 and N3, respectively).

Figure 5

Ligand interactions of compound 16 and VIR251 docked into the active site of SARS-CoV-2 PLpro ((A, B) 2D poses of compound 16 and VIR251; (C, D) 3D poses of compound 16 and VIR251, respectively).

Figure 6

Ligand interactions of compound 16 and remedesivir docked into the active site of SARS-CoV-2 RdRp ((A, B) 2D poses of compound 16 and remedesivir; (C, D) 3D poses of compound 16 and remedesivir, respectively).