Synthesis and evaluation of β-carbolinium cations as new antimalarial agents based on π-delocalized lipophilic cation (DLC) hypothesis

Kiyosei Takasu, Tsubasa Shimogama, Chalerm Saiin, Hye-Sook Kim, Yusuke Wataya, Reto Brun, Masataka Ihara

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Several β-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 β-carbolines and a good correlation was observed between π-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. β-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.

Original languageEnglish
Pages (from-to)653-661
Number of pages9
JournalChemical and Pharmaceutical Bulletin
Volume53
Issue number6
DOIs
Publication statusPublished - Jun 2005

Fingerprint

Carbolines
Antimalarials
Cations
Salts
Derivatives
Malaria
Rodentia
In Vitro Techniques

Keywords

  • β-Carbolinium salt
  • π-delocalized lipophilic cationic (DLC) hypothesis
  • Antimalarial agent
  • Structure-activity relationship
  • Total synthesis
  • Tropical disease

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Pharmacology

Cite this

Synthesis and evaluation of β-carbolinium cations as new antimalarial agents based on π-delocalized lipophilic cation (DLC) hypothesis. / Takasu, Kiyosei; Shimogama, Tsubasa; Saiin, Chalerm; Kim, Hye-Sook; Wataya, Yusuke; Brun, Reto; Ihara, Masataka.

In: Chemical and Pharmaceutical Bulletin, Vol. 53, No. 6, 06.2005, p. 653-661.

Research output: Contribution to journalArticle

Takasu, Kiyosei ; Shimogama, Tsubasa ; Saiin, Chalerm ; Kim, Hye-Sook ; Wataya, Yusuke ; Brun, Reto ; Ihara, Masataka. / Synthesis and evaluation of β-carbolinium cations as new antimalarial agents based on π-delocalized lipophilic cation (DLC) hypothesis. In: Chemical and Pharmaceutical Bulletin. 2005 ; Vol. 53, No. 6. pp. 653-661.
@article{5bb45bd2d7ec4cad856b26dac3a139f1,
title = "Synthesis and evaluation of β-carbolinium cations as new antimalarial agents based on π-delocalized lipophilic cation (DLC) hypothesis",
abstract = "Several β-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 β-carbolines and a good correlation was observed between π-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. β-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.",
keywords = "β-Carbolinium salt, π-delocalized lipophilic cationic (DLC) hypothesis, Antimalarial agent, Structure-activity relationship, Total synthesis, Tropical disease",
author = "Kiyosei Takasu and Tsubasa Shimogama and Chalerm Saiin and Hye-Sook Kim and Yusuke Wataya and Reto Brun and Masataka Ihara",
year = "2005",
month = "6",
doi = "10.1248/cpb.53.653",
language = "English",
volume = "53",
pages = "653--661",
journal = "Chemical and Pharmaceutical Bulletin",
issn = "0009-2363",
publisher = "Pharmaceutical Society of Japan",
number = "6",

}

TY - JOUR

T1 - Synthesis and evaluation of β-carbolinium cations as new antimalarial agents based on π-delocalized lipophilic cation (DLC) hypothesis

AU - Takasu, Kiyosei

AU - Shimogama, Tsubasa

AU - Saiin, Chalerm

AU - Kim, Hye-Sook

AU - Wataya, Yusuke

AU - Brun, Reto

AU - Ihara, Masataka

PY - 2005/6

Y1 - 2005/6

N2 - Several β-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 β-carbolines and a good correlation was observed between π-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. β-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.

AB - Several β-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 β-carbolines and a good correlation was observed between π-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. β-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.

KW - β-Carbolinium salt

KW - π-delocalized lipophilic cationic (DLC) hypothesis

KW - Antimalarial agent

KW - Structure-activity relationship

KW - Total synthesis

KW - Tropical disease

UR - http://www.scopus.com/inward/record.url?scp=21144445234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21144445234&partnerID=8YFLogxK

U2 - 10.1248/cpb.53.653

DO - 10.1248/cpb.53.653

M3 - Article

VL - 53

SP - 653

EP - 661

JO - Chemical and Pharmaceutical Bulletin

JF - Chemical and Pharmaceutical Bulletin

SN - 0009-2363

IS - 6

ER -