A Review on Antimalarial 1,2,4-Trioxane Derivatives

Malaria in recent years becomes a major health hitch globally due to the surfacing of multidrug-resistant strains of Plasmodium falciparum parasite. In recent times, artemisinin (ART)-based drugs and combination therapies become the drugs of preference for the treatment and prophylaxis of resistant P. falciparum malaria. Endoperoxide compounds natural, semi-synthetic or synthetic signifying a massive number of antimalarial agents which possess a wide structural miscellany with needed antimalarial effectiveness against resistant P. falciparum malaria. The 1,2,4-trioxane ring system deficient the lactone ring which constitutes the most significant endoperoxide structural scaffold which is believed to be the key pharmacophoric moiety and is principally responsible for the pharmacodynamic potential of endoperoxide-based antimalarials. This becomes the main reason for the research related to endoperoxide particularly 1,2,4-trioxane-, 1,2,4-trioxolane- and 1,2,4,5-tetraoxane-based scaffolds gaining the noteworthy interest in recent years for developing antimalarial drugs against resistant malaria. In this paper, a comprehensive endeavour has been made to review the development of different endoperoxide antimalarial agents and structural diversity of endoperoxide molecules derived from 1,2,4-trioxane- based structural scaffolds. Keywords: Endoperoxide; 1,2,4-trioxane; pharmacophores; artemisinin; antimalarial.