title: Synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (DLC) hypothesis.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan. kay-t@mail.pharm.tohoku.ac.jp
authors.forename: Kiyosei
authors.initials: K
authors.lastname: Takasu
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Shimogama
authors.forename: Chalerm
authors.initials: C
authors.lastname: Saiin
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Wataya
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Masataka
authors.initials: M
authors.lastname: Ihara
mesh_terms: 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
chemical_list: D000962:Antimalarials; D002243:Carbolines