Advances in the research on the targets of anti-malaria actions of artemisinin

Abstract

Malaria has been a global epidemic health threat since ancient times. It still claims roughly half a million lives every year in this century. Artemisinin and its derivatives, are frontline antimalarial drugs known for their efficacy and low toxicity. After decades of wide use, artemisinins remain our bulwark against malaria. Here, we review decades of efforts that aim to understand the mechanism of action (MOA) of artemisinins, which help explain the specificity and potency of this anti-malarial drug. We summarize the methods and approaches employed to unravel the MOA of artemisinin over the last three decades, showing how the development of advanced techniques can help provide mechanistic insights and resolve some long-standing questions in the field of artemisinin research. We also provide examples to illustrate how to better repurpose artemisinins for anti-cancer therapies by leveraging on MOA. These examples point out a practical direction to engineer artemisinin for broader applications beyond malaria.

Currently Available Strategies for Target Identification of Bioactive Natural Products

“…Furthermore, many research groups have used radio-labeled or fluorescent-labeled probes to identify the targets of a range of bioactive NPs, such as the flavonoid 7-O-cinnamoyl paclitaxel ( Gunesch et al, 2020 ) , xanthohumol from hops ( Brodziak-Jarosz et al, 2016 ) , and artemisinin ( Yang J. et al, 2020 ) . Cephalosporin I, which was recently synthesized by Amatuni’s group using facile chemoenzymatic synthesis, exhibited selectivity for proteasome subunits β2 and β5 after the introduction of fluorescent labels.…”

Antiprotozoal and Antitumor Activity of Natural Polycyclic Endoperoxides: Origin, Structures and Biological Activity

“…As shown in recent years, many polycyclic endoperoxides, both natural and synthetic, have antimalarial effects [ 21 , 22 ]. It is known that malaria or “swamp fever” refers to a group of transmissible infectious diseases transmitted to humans by bites of female mosquitoes belonging to the genus Anopheles, caused by parasitic protists of the genus Plasmodium, mainly P. falciparum [ 23 , 24 , 25 ].…”

Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment

“…Through extensive research on artemisinin, researchers revealed that its primary anti-malarial activity is due to special internal structures called endoperoxide linkages (peroxide bridges) [ 33 ]. When the malaria parasites invade the human body, they digest a large amount of hemoglobin in host erythrocytes to obtain the nutrients necessary for growth and maturation.…”