The Amaryllidaceae as a source of antiplasmodial crinane alkaloid constituents.

Malaria is prevalent in tropical and subtropical regions of the globe. With over 200 million cases reported annually, particularly in sub-Saharan Africa, it is an unnecessary burden to already overworked and ailing healthcare structures. Traditional medicine (TM) remains vibrant in most of these regions wherein plants often serve as the first line of defense against malaria. Given this fact as well as the successes elsewhere of therapies such as Artemisia annua emanating from evidence-based TM, interest in plants as a source of new antimalarial drugs has been rejuvenated. The bulbous plant family Amaryllidaceae is recognized for its structurally-diverse alkaloid constituents which exhibit interesting biological properties. This review focuses on the in vitro activities demonstrated by its crinane alkaloids against various strains of the malaria-causing parasite Plasmodium falciparum. The survey embraces the twelve genera of the Amaryllidaceae whose nineteen representative species have been examined for antiplasmodial crinane alkaloid principles. A total of seventy-two compounds were screened against nine strains of P. falciparum, with the α-crinanes reflecting better overall activities than their corresponding β-crinane subgroup congeners. In terms of potency, an ED ₅₀ of 0.14 μg/mL (for augustine in the D-6 strain) and IC ₅₀ of 0.35 μg/mL (for haemanthidine in the K1 strain) were the lowest activity indices observed. Structure-activity relationship studies afforded useful insight on the antiplasmodial pharmacophore and the features supporting its efficacy. Overall, crinane alkaloids have provided a useful platform for the study of antiplasmodial effects, not only in terms of potency but also in terms of structural diversity.
(Copyright © 2019 Elsevier B.V. All rights reserved.)