Antimalarial peroxides: advances in drug discovery and design

Singlet oxygen and natural substrates: functional polyunsaturated models for the photooxidative degradation of carotenoids

“…The interest in this field of photochemistry arises from the search in effective antimalarial peroxides, an intensively investigated area in medicinal chemistry [49]. The natural sesquiterpene peroxide artemisinin (qinghaosu), used since centuries in Chinese folk medicine as a plant extract, has initiated and stimulated this field of research [50].…”

Peroxy natural products

“…Its antimalarial activity, structural modification, structure-activity relationships, mode of actions, and use in therapy have been well reviewed. [237][238][239][240] 3.3 Diterpenes: A dolabellane diterpene derivative 401 with the naturally rare peroxy function was identified as a component of the aerial parts of Cleome droserifolia, 241 and additional related peroxide 402 was found from Aglaia odorata. 242 Jatropha integerrima provided a rhamnofolane endoperoxide 2-epicaniojane 403, whose structure was confirmed by X-ray diffraction analysis.…”

Antimalarial chemotherapy: Artemisinin-derived dimer carbonates and thiocarbonates

“…23 Tethering two artemisinin units together through the C10 position forms a C10 non-acetal dimeric trioxane structure, which has proven often to be more antimalarially potent than its corresponding monomeric counterpart. 24–26 We have highlighted the high efficacy of a low single oral dose ACT using new artemisinin-derived trioxane dimers with linkers of different length: 5-carbon ( 7 ), 27 4-carbon ( 8 ), 28 3-carbon ( 9 ), 29,30 and 2-carbon ( 10 , Figure 2).…”