Therapeutical Utilization and Repurposing of Artemisinin and Its Derivatives: A Narrative Review

Abstract

Artemisinin (ART) and its derivatives have great therapeutical utility as antimalarials and can be repurposed for other indications, such as viral infections, autoimmune diseases, and cancer. This review presents a comprehensive overview of the therapeutic effects of ART‐based drugs, beyond their antimalarial effects. This review also summarizes the information on their repurposing in other pathologies, with the hope that it will guide the future optimization of the use of ART‐based drugs and of the treatment strategies for the listed diseases. By reviewing related literature, ART extraction and structure as well as the synthesis and structure of its derivatives are presented. Subsequently, the traditional roles of ART and its derivatives against malaria are reviewed, including antimalarial mechanism and occurrence of antimalarial resistance. Finally, the potential of ART and its derivatives to be repurposed for the treatment of other diseases are summarized. The great repurposing potential of ART and its derivatives may be useful for the control of emerging diseases with corresponding pathologies, and future research should be directed toward the synthesis of more effective derivatives or better combinations.

Micromolar Dihydroartemisinin Concentrations Elicit Lipoperoxidation in Plasmodium falciparum-Infected Erythrocytes

“…In this study, 4-HNE formation and conjugation with proteins were provoked by micromolar DHA concentrations, at which DHA exerts antitumor activity [28,29]. The molecular mechanism of DHA action against tumors is largely unknown, and we propose 4-HNE binding to functionally relevant proteins as the molecular mechanism through which DHA might control tumor progression.…”

“…Moreover, the efficient antimalarial drug DHA was proposed as a potential drug for treating malignancies, inflammatory conditions, and other diseases as well [28,29]. Mechanistic studies of antitumor activity of DHA in HCT116 colorectal and NCI-H460 lung adenocarcinoma cells revealed lipid peroxidation in response to 50 µM DHA by BODIPY-C11 fluorescent probe and protein oxidation, which resulted in mitochondrial damage and eventually in iron-dependent cell death [30].…”

Repurposing of anti-malarial drugs for the treatment of tuberculosis: realistic strategy or fanciful dead end?

“…QuinineLeg cramps Off-label use for the treatment of nocturnal leg cramps, although this use is controversial due to potential adverse effects[21] Primaquine Pneumocystis jiroveci Pneumonia (PCP) In combination with clindamycin as salvage treatment of PCP[22] Artemisinins Cancer Studies suggest that these compounds can induce apoptosis (programmed cell death) in cancer cells[23,24] Inflammatory diseases Investigated for RA, SLE, and othersSchistosomiasisEffective against young helminths (potential for combination therapy with praziquantel), also in combination with 4-aminoquinolines (see above)Viral Infections Potential antiviral effects against a range of viruses, including Hepatitis B and C, human herpesvirus, and others (not clinically confirmed)…”