Planta Med 2019; 85(08): 637-647
DOI: 10.1055/a-0880-5414
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antiplasmodial Lycorane Alkaloid Principles of the Plant Family Amaryllidaceae

Jerald J. Nair
Research Centre for Plant Growth and Development, University of KwaZulu-Natal Pietermaritzburg, Scottsville, South Africa
,
Johannes van Staden
Research Centre for Plant Growth and Development, University of KwaZulu-Natal Pietermaritzburg, Scottsville, South Africa
› Author Affiliations
Further Information

Publication History

received 17 January 2019
revised 12 March 2019

accepted 14 March 2019

Publication Date:
25 March 2019 (online)

Abstract

The spread of malaria is thought to have followed human expansion out of Africa some 60 – 80 thousand years ago. With its prevalence in pantropical countries of the world and epicenter localized in Africa, malaria is now considered an unnecessary burden to overworked and under-resourced healthcare structures. Plants have long afforded a fertile hunting ground for the search and identification of structurally diverse antimalarial agents, such as quinine and artemisinin. This survey examines the antiparasitic properties of the family Amaryllidaceae via the antiplasmodial activities demonstrated for its lycorane alkaloid principles. Of these, 24 were natural compounds identified in 20 species from 11 genera of the Amaryllidaceae family, whilst the remaining 28 were synthetically derived entities based on the lycorane skeleton. These were screened against ten different strains of the malarial parasite Plasmodium falciparum, wherein the parent compound lycorine was shown to be the most potent with an IC50 of 0.029 µg/mL in the FCR-3 strain seen to be the best. Structure-activity relationship studies revealed that good activities were detectable across both the natural compounds as well as the synthetically accessed derivatives. Such studies also highlighted that there are several inherent structural features that define the lycorane alkaloid antiplasmodial pharmacophore, such as the nature of its ring systems and properties of its substituents. Mechanistically, a limited number of studies confirmed that lycorane alkaloids manifest their action by targeting enzymes associated with the plasmodial FAS-II biosynthetic pathways. Overall, these alkaloids have provided useful, convenient, and accessible scaffolds for antimalarial-based drug discovery.

 
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