Biosynthesis and Biological Activities of Newly Discovered Amaryllidaceae Alkaloids

Abstract

Alkaloids are an important group of specialized nitrogen metabolites with a wide range of biochemical and pharmacological effects. Since the first publication on lycorine in 1877, more than 650 alkaloids have been extracted from Amaryllidaceae bulbous plants and clustered together as the Amaryllidaceae alkaloids (AAs) family. AAs are specifically remarkable for their diverse pharmaceutical properties, as exemplified by the success of galantamine used to treat the symptoms of Alzheimer's disease. This review addresses the isolation, biological, and structure activity of AAs discovered from January 2015 to August 2020, supporting their therapeutic interest.

Keywords: Amaryllidaceae alkaloids; anti-cholinesterase; antiparasitic; antitumor; antiviral; biosynthesis; specialized metabolism.

Figure 1

Representative Amaryllidaceae alkaloid structure for the main Amaryllidaceae alkaloid (AA)-types.

Figure 2

Biosynthesis pathway to major types of Amaryllidaceae alkaloids. Arrows without labeling reflect chemical reactions that have not been enzymatically characterized. Enzymes that have been identified are labeled in blue. A solid arrow symbolizes one enzymatic step whereas a broken arrow shows multiple enzymatic reactions. Chemical structures of precursors were added to clarify the regioselective phenol-phenol’ coupling reaction. Enzyme abbreviations: PAL, phenylalanine ammonia-lyase; C4H, cinnamate 4-hydroxylase; C3H, coumarate 3-hydroxylase; APX, ascorbate peroxidase; HBS, 4-hydroxybenzaldehyde synthase; TYDC, tyrosine decarboxylase; NBS, norbelladine synthase; NR, noroxomaritidine reductase; CYP96T1, cytochrome P450 monooxygenase 96T1.

Figure 3

Chemical structure of novel Amaryllidaceae alkaloids of the norbelladine- (1–6), cherylline (7–8) and galantamine-type (9–16). Numbers in bold refer to the compounds depicted in Table 2.

Figure 4

Chemical structure of new alkaloids of the lycorine- (17–25) and homolycorine-type (26–30). Numbers in bold refer to the compounds depicted in Table 2.

Figure 5

Chemical structure of new alkaloids crinine-, narciclasine-, tazettine-, and montanine-type (31–55). Numbers in bold refer to the compounds depicted in Table 2.

Figure 6

Chemical structure of new alkaloids plcamine-, seco-plicamine-, cripowellin-, and mesembrine-type. Numbers in bold refer to the compounds depicted in Table 2.

Figure 7

Chemical structure of new alkaloids of other types. Numbers in bold refer to the compounds depicted in Table 2.