An overview on the antimalarial activity of 1,2,4‐trioxanes, 1,2,4‐trioxolanes and 1,2,4,5‐tetraoxanes

Abstract

The demand for novel, fast‐acting, and effective antimalarial medications is increasing exponentially. Multidrug resistant forms of malarial parasites, which are rapidly spreading, pose a serious threat to global health. Drug resistance has been addressed using a variety of strategies, such as targeted therapies, the hybrid drug idea, the development of advanced analogues of pre‐existing drugs, and the hybrid model of resistant strains control mechanisms. Additionally, the demand for discovering new potent drugs grows due to the prolonged life cycle of conventional therapy brought on by the emergence of resistant strains and ongoing changes in existing therapies. The 1,2,4‐trioxane ring system in artemisinin (ART) is the most significant endoperoxide structural scaffold and is thought to be the key pharmacophoric moiety required for the pharmacodynamic potential of endoperoxide‐based antimalarials. Several derivatives of artemisinin have also been found as potential treatments for multidrug‐resistant strain in this area. Many 1,2,4‐trioxanes, 1,2,4‐trioxolanes, and 1,2,4,5‐tetraoxanes derivatives have been synthesised as a result, and many of these have shown promise antimalarial activity both in vivo and in vitro against Plasmodium parasites. As a consequence, efforts to develop a functionally straight‐forward, less expensive, and vastly more effective synthetic pathway to trioxanes continue. This study aims to give a thorough examination of the biological properties and mode of action of endoperoxide compounds derived from 1,2,4‐trioxane‐based functional scaffolds. The present system of 1,2,4‐trioxane, 1,2,4‐trioxolane, and 1,2,4,5‐tetraoxane compounds and dimers with potentially antimalarial activity will be highlighted in this systematic review (January 1963–December 2022).

Unprecedented POSS‐Linked 3D Covalent Organic Frameworks with 2‐Fold Interpenetrated scu or sqc Topology Regulated by Porphyrin Center for Photocatalytic CO2 Reduction

“…Artemisinin has garnered considerable attention due to its unique trioxane structure and exceptional antimalarial properties [49] . However, its production cost remains prohibitively high.…”

“…Artemisinin has garnered considerable attention due to its unique trioxane structure and exceptional antimalarial properties. [49] However, its production cost remains prohibitively high. The primary expense arises from the oxygenation process of dihydroartemisinic acid (DHAA), which necessitates replicating the plant's synthetic pathway.…”

Formulation and Characterization of GDL-Based Artesunate Solid Lipid Nanoparticle

“…Solid lipid nanoparticles (SLNs) are identical to o/w emulsion, except the liquid lipid is replaced by solid lipids at room temperature. Both hydrophilic and hydrophobic drugs can be incorporated into SLNs [11]. Various advantages offered by SLNs include small size, greater surface area, enhanced bioavailability, high drug loading, protection of active pharmaceutical ingredients, and enhanced penetration of topical preparation.…”