Background: Fungal pathogenesis continues to be a burden to healthcare structures in both developed and developing nations. The gradual and irreversible loss of efficacies of existing antifungal medicines as well as the emergence of drug-resistant strains have contributed largely to this scenario. There is therefore a pressing need for new drugs from diverse structural backgrounds with improved potencies and novel modes of action to fortify or replace contemporary antifungal schedules.

Aim: Alkaloids of the plant family Amaryllidaceae exhibit good growth inhibitory activities against several fungal pathogens. This review focuses on the mechanistic aspects of these antifungal activities. It achieves this by highlighting the molecular targets as well as structural features of Amaryllidaceae constituents which serve to enhance such action.

Methods: During the information gathering stage extensive use was made of the three database platforms; Google Scholar, SciFinder and Scopus. In most instances articles were accessed directly from journals licensed to the University of KwaZulu-Natal. In the absence of such proprietary agreements the respective corresponding authors were approached directly for copies of papers.

Results: Although several classes of molecules from the Amaryllidaceae have been probed for their antifungal effects, it is the key constituents lycorine and narciclasine which have together afforded the most profound mechanistic insights. These may be summarized as follows: (i) effects on the fungal cell wall and cell membrane; (ii) effects on morphology such as budding and hyphal growth; (iii) effects on fungal organelles such as ribosomes; (iv) effects on macromolecules such as DNA, RNA and proteins and; (v) identification of the active sites for these constituents.

Conclusion: The key feature in the antifungal effects of Amaryllidaceae alkaloids is the inhibition of protein synthesis. This involved the inhibition of peptide bond formation by binding to yeast ribosomes via the 60S subunit. Related effects involved the inhibition of both DNA and RNA synthesis. These adverse effects were reflected morphologically on both the fungal cell wall and cell membrane. Such observations should prove useful in the chemotherapeutic arena should efforts shift towards the development of a clinical candidate.

• PMID: 30773353
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Reference Type

Journal Article | Review

Authors

Nair JJ, van Staden J

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Review For