Progress in the development of peroxide-based anti-parasitic agents

Although unmatchable in their fast clinical response, first generation artemisinin analogs have short biological half-lives, a drawback that results in recrudescence. Efforts during the past decade have identified a number of new artemisinin derivatives with superior therapeutic profiles. As parasitic infections are more prevalent in underdeveloped nations, cost effectiveness during large-scale production of drug candidates remains as the key factor that can affect their success. Apart from compounds that retain an artemisinin core, information pertaining to the mode of action of this natural product has been helpful in the development of new synthetic peroxides with promising biological activities. A commendable success in this area is the compound OZ277 (or RBx-11160)—an orally active synthetic ozonide. A combination of this drug with piperaquine has been selected for phase III clinical trials. Related studies have shown that parasites belonging to genera such as leishmania, schistosoma, trypanosoma and toxoplasma are also susceptible to the artemisinin class of compounds, showing their potential as broad-spectrum anti-infective agents. In addition to artemisinin, a large number of peroxide-containing natural products with interesting biological properties have been isolated from plant and marine sources. Structure-optimization and structure–activity relationship studies involving these new skeletons hold lot of promise in the area of peroxide-based anti-infective agents.