Applicability of Redirecting Artemisinins for New Targets

Employing new therapeutic indications for drugs that are already approved for human use has obvious advantages, including reduced costs and timelines, because some routine steps of drug development and regulation are not required. This work concentrates on the redirection of artemisinins (ARTS) that already are approved for clinical use, or investigated, for malaria treatment. Several mechanisms of action are suggested for ARTS, among which only a few have been successfully examined in vivo, mainly the induction of oxidant stress and anti-inflammatory effects. Despite these seemingly contradictory effects, ARTS are proposed for repurposing in treatment of inflammatory disorders and diverse types of diseases caused by viral, bacterial, fungal, and parasitic infections. When pathogens are treated the expected outcome is diminution of the causative agents and/or their inflammatory damage. In general, repurposing ARTS is successful in only a very few cases, specifically when a valid mechanism can be targeted using an additional therapeutic agent and appropriate drug delivery. Investigation of repurposing should include optimization of drug combinations followed by examination in relevant cell lines, organoids, and animal models, before moving to clinical trials. Repurposing of drugs has great practical appeal. However, a systematic approach is essential. Here, artemisinins (ARTS) are used to illustrate some considerations that are critical in this process. Several mechanisms of action are suggested for ARTS, among which only a few are successfully examined in vivo, mainly the induction of oxidant stress and anti-inflammatory effects. Consequently, ARTS are proposed for repurposing in treatment of inflammatory disorders and diverse types of diseases caused by viral, bacterial, fungal, and parasitic infections. In general, repurposing ARTS is successful in only a very few cases, specifically when a valid mechanism can be targeted, with the use of an additional therapeutic agent and appropriate drug delivery.image