Background: Despite the successes achieved recently in the treatment of various infectious diseases,
the morbidity and mortality associated with malaria remain major burdens.
Objective: The main limitations of conventional malaria therapy are the development of multi-drug resistance
resulting in high dosage of different drugs and subsequent pill burden and toxicity. Thus, new effective antimalarial
agents are urgently needed due to the increasing drug resistance of Plasmodium sp.
Discussion: Nature is successful in providing mankind with compounds against infectious diseases. Many of
small drugs on the market were originally developed from natural-based compounds. Scaffolds, such as monoor
diazanaphthalenes, naphthoquinone, indole, pyrrole or endoperoxides can be considered as privileged structures
for the discovery of new antimalarials. Nevertheless, some difficulties associated with natural lead compounds
derived from these scaffolds, such as their synthesis, limited aqueous solubility, chemical or metabolic
instability and wide spectrum of biological effects are needed to be solved.
Conclusion: Thus, semisynthetic or synthetic analogues of natural antimalarial agents exhibiting optimized
physicochemical properties, more selective biological activity and/or higher potency especially against resistant
or multidrug resistant strains have been designed. The review is focused on selected recently reported potential
antimalarial agents derived from isolated bioactive natural compounds based on the above-mentioned
scaffolds. Their mechanism of action and structure-activity relationships are briefly mentioned.