Cholinesterase Inhibition Activity, Alkaloid Profiling and Molecular Docking of Chilean Rhodophiala (Amaryllidaceae)

Abstract

Amaryllidaceae plants are the commercial source of galanthamine, an alkaloid approved for the clinical treatment of Alzheimer’s disease. The chemistry and bioactivity of Chilean representatives of Rhodophiala genus from the family of Amaryllidaceae have not been widely studied so far. Ten collections of five different Chilean Rhodophiala were analyzed in vitro for activity against enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) as well as for their alkaloid composition by GC-MS. To obtain an insight into the potential AChE and BuChE inhibitory activity of the alkaloids identified in the most active samples, docking experiments were carried out. Although galanthamine was found neither in aerial parts nor in bulbs of R. splendens, these plant materials were the most active inhibitors of AChE (IC₅₀: 5.78 and 3.62 μg/mL, respectively) and BuChE (IC₅₀: 16.26 and 14.37 μg/mL, respectively). Some 37 known alkaloids and 40 still unidentified compounds were detected in the samples, suggesting high potential in the Chilean Amaryllidaceae plants as sources of both novel bioactive agents and new alkaloids.

Keywords: AChE; BuChE; GC-MS; Rhodophiala; alkaloids; molecular docking.

Figure 1

Amaryllidaceae alkaloid types.

Figure 2

Map of Chile showing the collection sites of the Rhodophiala species. 1: Arcos de Calán; 2: Laguna del Maule; 3: Nevado de Chillán; 4: Las Trancas; 5: Volcán Lonquimay; 6: Malalcahuello; 7: Sierra Nevada. Map source: Google Earth.

Figure 3

Flowering Rhodophiala species from central-southern Chile. (A) R. andicola (Poepp.) Traub; (B) R. araucana (Phil.) Traub; (C) R. montana (Phil.) Traub; (D) R. splendens (Renjifo) Traub; (E) R. pratensis (Poepp.) Traub.; (F) R. pratensis white flowers and (G) R. pratensis plants with red and white flowers.

Figure 4

Alkaloids identified in Chilean Rhodophiala species by GC-MS.

Figure 5

GC chromatograms of the alkaloids from Chilean Rhodophiala species. Numbers refer to Table 2. (A) Bulbs of R. andicola (Sierra Nevada); (B) Aerial parts of R. andicola (Sierra Nevada); (C) Bulbs of R. andicola (Nevado de Chillán); (D) Aerial parts of R. andicola (Nevado de Chillán). IS: internal standard; U: unknown.

Figure 6

GC chromatograms of the alkaloids from Chilean Rhodophiala species. Numbers refer to Table 2. (E) Bulbs of R. andicola (Volcán Lonquimay); (F) Aerial parts of R. andicola (Volcán Lonquimay); (G) Bulbs of R. araucana; (H) Aerial parts of R. araucana. IS: internal standard; U: unknown.

Figure 7

GC chromatograms of the alkaloids from Chilean Rhodophiala species. Numbers refer to Table 2. (I) Bulbs of R. montana; (J) Aerial parts of R. montana; (K) Bulbs of R. pratensis (red flowers, without leaves, growing on sand dunes); (L) Aerial parts of R. pratensis (red flowers, without leaves, growing on sand dunes). IS: internal standard; U: unknown.

Figure 8

GC chromatograms of the alkaloids from Chilean Rhodophiala species. Numbers refer to Table 2. (M) Bulbs of R. pratensis (red flowers, with leaves); (N) Aerial parts of R. pratensis (red flowers, with leaves); (O) Bulbs of R. pratensis (red flowers, without leaves); (P) Aerial parts of R. pratensis (red flowers, without leaves). IS: internal standard; U: unknown.

Figure 9

GC chromatograms of the alkaloids from Chilean Rhodophiala species. Numbers refer to Table 2. (Q) Bulbs of R. pratensis (white flowers); (R) Aerial parts of R. pratensis (white flowers); (S) Bulbs of R. splendens; (T) Aerial parts of R. splendens. IS: internal standard; U: unknown.

Figure 10

Graphical representations of the binding of (a) 11-hydroxivittatine (20a) and (b) hamayne (20b) in the gorge of the active site of hBuChE.