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.
Key words
alkaloid - amaryllidaceae - antiplasmodial - malaria - medicinal plant
