Synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (DLC) hypothesis.
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.
Takasu
Kiyosei
K
Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan. kay-t@mail.pharm.tohoku.ac.jp
Shimogama
Tsubasa
T
Saiin
Chalerm
C
Kim
Hye-Sook
HS
Wataya
Yusuke
Y
Brun
Reto
R
Ihara
Masataka
M
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008288:Malaria / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010962:Plasmodium berghei / Q000187:drug effects
D000962:Antimalarials; D002243:Carbolines