Expanding the therapeutic spectrum of artemisinin: Activity against infectious diseases beyond malaria and novel pharmaceutical developments

The interest of Western medicine in Traditional Chinese Medicine (TCM) as a source of drug leads/new drugs to treat diseases without available efficienttherapieshasbeendramaticallyaugmentedinthelastdecadesbytheextensiveworkandtheoutstandingfindingsachievedwithinthiskind ofmedicine.ThepracticeofTCMoverthousandsofyearshasequippedscientistswithsubstantialexperiencewithhundredsofplantsthatledtothe discovery of artemisinin (qinghaosu), which is extracted from the medicinal plant Artemisia annua L. (qinghao). The unexpected success of artemisinin in combatingmalariahas drawn strongattentionfromthe scientificcommunity towardsTCM. Artemisinin was discovered byYouyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives (artemisinins) exert profound activities towards other protozoans (Leishmania, Trypanosoma, amoebas,Neospora caninum, andEimeria tenella), trematodes (Schistosoma, liver flukes), and viruses (human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives (artesunate, artemether, arteether), novel drug development strategies have been pursued. These included the synthesis of acetal- and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, e.g. artemisinin-basedliposomes,niosomes,micelles,solidlipidnanocarriers,nanostructuredlipidcarriers,nanoparticles,fullerenesandnanotubes.The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types ofinfectiouspathogensthataresusceptibletoartemisininsinvitroandinvivo,inadditiontotheadvancementintheirdrugdeliverysystemsutilizing pharmaceutical technology. It would be expected that different therapeutic strategies based on the second and third generation artemisinin derivatives and artemisinin-based drug technologies would be available in the near future to treat specific infectious diseases.