Life has a prodigious capacity to overcome death, and this is exactly emblematic of drug resistance, one of the biggest threats for health systems, clinicians, researchers and patients. Several decades of intense and innovative drug discovery and development were not able to prevent the loss of medicines owing to resistance among viruses, bacteria and parasites. The common denominator to drug resistance is the ability of the targeted microorganisms to select the very few of them that can overcome the selective pressure and grow, often as a result of mutations occurring in genes coding for either drug targets, drug transporters and efflux pumps, or drug degradation systems. In the context of malaria, even the latest generation of drugs, such as the artemisinins that were not supposed to act through a unique target and thus able to resist resistance mechanisms, has started to lose their full efficacy in patients. In wild‐type parasites, the endoperoxide bond of artemisinin and its derivatives is cleaved in the presence of haem‐Fe2+ liberated from proteolyzed haemoglobin. Two processes have been described; the first generates oxygen radicals, which, via hydrogen atom abstraction or β‐scission processes, lead to carbon‐based radicals that can form covalent bonds with proteins and lipids in close vicinity. The second process involves a two‐electron heterolytic cleavage, in which the peroxide's oxidation potential causes death of the parasite (Haynes et al , 2013). The resulting alkylations or oxidative stress become extremely toxic to the parasite and inactivate vital functions. The cleavage of endoperoxides occurs mainly in the parasite's trophozoite blood stage where haemoglobin proteolysis takes place, and in very young ring stages, which makes artemisinins and all endoperoxides fast‐acting molecules. Most of the endoperoxides, with the exception of the ozonide OZ439, are short‐lasting molecules. Once activated, artemisinins and endoperoxides kill parasites very fast, making them extremely …