Synthesis and antimalarial activity of 6-cycloalkylvinyl substituted 1,2,4-trioxanes

Recent advances in antimalarial drug development

“…It has progressed through preclinical regulatory studies and advanced to preclinical studies. Singh et al 97,98 have made significant contributions in the synthesis of small synthetic 1,2,4-trioxanes and their recent efforts led to the easy and affordable synthesis of orally effective 6-alkylvinyl/arylalkylvinyl/cycloalkylvinyl substituted 1,2,4-trioxanes of general structure 14 (see Fig. 3).…”

“…Exposure to powerful iron chelators is found to limit the size of this pool, thus reducing the rate of incorporation of iron into critical redox proteins and metalloenzymes. This mechanism is likely to be associated with the hexadentate chelators, for instance desferrioxamine (98), synthetic trihydroxamates (99), and HBED (101). It is well known that the stable crystalline structure of hemozoin is critically important for the viability of the parasite, as the dissociated heme is potentially toxic to the parasite, due to the generation of hydroxyl radicals under aerobic conditions.…”

A sensitive and selective liquid chromatographic tandem mass spectrometric assay for simultaneous quantification of novel trioxane antimalarials in different biomatrices using sample-pooling approach for high throughput pharmacokinetic studies☆

“…CDRI in its drug discovery program has developed promising antimalarial compounds 99-357, 99-408 and 99-411 of this class ( Fig. 1) [6][7][8][9][10][11]. These candidates will be subjected to in vitro and in vivo pharmacokinetic (PK) screening for selecting promising candidates for further development.…”

A high throughput approach for simultaneous estimation of multiple synthetic trioxane derivatives using sample pooling for pharmacokinetic studies

“…The size of the sample pool that could be employed under the sample pooling concept depends entirely on the selectivity, specificity and sensitivity of the bioassay developed. In the present method the applicability of conventional bioanalytical techniques like HPLC-UV to sample pooling concept is described using three novel 1,3,4-trioxane antimalarials of artemisinin class [7][8][9][10][11][12], 99/408, 99/411 and 99/357, developed at Central Drug Research Institute (CDRI), Lucknow.…”