1380688-07-2Relevant academic research and scientific papers
Evaluation of Bis-Alkylamidoxime O-Alkylsulfonates as Orally Available Antimalarials
Degardin, Melissa,Wein, Sharon,Gouni, Smitha,Tran Van Ba, Christophe,Duckert, Jean-Frederic,Durand, Thierry,Escale, Roger,Vial, Henri,Vo-Hoang, Yen
, p. 991 - 1001 (2012)
The main threat to controlling malaria is the emerging multidrug resistance of Plasmodiumsp. parasites. Bis-alkylamidines were developed as a potential new chemotherapy that targets plasmodial phospholipid metabolism. Unfortunately, these compounds are not orally available. To solve this absorption issue, we investigated a prodrug strategy based on sulfonate derivatives of alkylamidoximes. A total of 25 sulfonates were synthesized as prodrug candidates of one bis-N-alkylamidine and of six N-substituted bis-C-alkylamidines. Their antimalarial activities were evaluated invitro against P. falciparum and invivo against P. vinckei in mice to define structure-activity relationships. Small alkyl substituents on the sulfonate group of both C-alkyl- and N-alkylamidines led to the best oral antimalarial activities; alkylsulfonate derivatives are chemically transformed into the corresponding alkylamidines.
