Abstract
The alkaloids characteristically produced by the subfamily Amaryllidoideae of the Amaryllidaceae, bulbous plant species that include well know genera such as Narcissus (daffodils) and Galanthus (snowdrops), are a source of new pharmaceutical compounds. Presently, only the Amaryllidaceae alkaloid galanthamine, an acetylcholinesterase inhibitor used to treat symptoms of Alzheimer’s disease, is produced commercially as a drug from cultivated plants. However, several Amaryllidaceae alkaloids have shown great promise as anti-cancer drugs, but their further clinical development is restricted by their limited commercial availability. Amaryllidaceae species have a long history of cultivation and breeding as ornamental bulbs, and phytochemical research has focussed on the diversity in alkaloid content and composition. In contrast to the available pharmacological and phytochemical data, ecological, physiological and molecular aspects of the Amaryllidaceae and their alkaloids are much less explored and the identity of the alkaloid biosynthetic genes is presently unknown. An improved molecular understanding of Amaryllidaceae alkaloid biosynthesis would greatly benefit the rational design of breeding programs to produce cultivars optimised for the production of pharmaceutical compounds and enable biotechnology based approaches.
Highlights
The chemically diverse alkaloids represent a large group of plant defence compounds which are characterised by containing a nitrogen atom in a heterocyclic ring [1]
Opium poppy produces more than 50 different alkaloids, and special cultivars have been developed for the production of, for instance, thebaine [122], which is used for the semi-synthesis of such compounds, like oxycodone, and these cultivars produce very little morphine
Galanthamine is presently produced commercially from cultivated Amaryllidaceae as a drug for the symptomatic treatment of Alzheimer’s disease, and other Amaryllidaceae alkaloids are of interest for pharmaceutical drug development
Summary
The chemically diverse alkaloids represent a large group of plant defence compounds which are characterised by containing a nitrogen atom in a heterocyclic ring [1]. The research efforts to support commercial production include organic chemistry approaches to obtain partial or full chemical synthesis, production in cell or tissue culture, domestication and improved cultivation methods, development of new cultivars, and molecular methods to identify the biosynthetic genes and potentially establish production in heterologous systems [2,3,4]. Due to their complex stereochemistry, the organic synthesis of alkaloids of pharmaceutical interest is often highly challenging and not always economically viable. We review aspects of the Amaryllidaceae and their alkaloids ranging from chemical ecology to commercial production and discuss research challenges and opportunities
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