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Synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic
Kiyosei Takasu1, Tsubasa Shimogama, Chalerm Saiin
1Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan. kay-t@mail.pharm.tohoku.ac.jp
Abstract:
Several beta-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. A tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. Quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral beta-carbolines and a good correlation was observed between pi-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. beta-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.
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