Mono- and Bis-Thiazolium Salts Have Potent Antimalarial Activity

Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibit...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2005-05, Vol.48 (10), p.3639-3643
Main Authors: Hamzé, Abdallah, Rubi, Eric, Arnal, Pascal, Boisbrun, Michel, Carcel, Carole, Salom-Roig, Xavier, Maynadier, Marjorie, Wein, Sharon, Vial, Henri, Calas, Michèle
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Antiparasitic agents
Biological and medical sciences
Chemical Sciences
Female
Malaria - drug therapy
Medical sciences
Mice
Organic chemistry
Pharmacology. Drug treatments
Plasmodium
Plasmodium falciparum - drug effects
Structure-Activity Relationship
Thiazoles - chemical synthesis
Thiazoles - chemistry
Thiazoles - pharmacology
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Summary:Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC50 values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED50 ≤ 0.22 mg/kg), and low toxicity in mice infected by Plasmodium vinckei.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm0492608