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 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50) </= 0.22 mg/kg), and low toxicity in mice infected by Plasmodium vinckei.
Hamzé
Abdallah
A
Laboratoire des Amino acides Peptides et Protéines (LAPP) CNRS-UMR 5810, CP 19, Université Montpellier I, Place E. Bataillon, 34095 Montpellier Cedex 5, France.
Rubi
Eric
E
Arnal
Pascal
P
Boisbrun
Michel
M
Carcel
Carole
C
Salom-Roig
Xavier
X
Maynadier
Marjorie
M
Wein
Sharon
S
Vial
Henri
H
Calas
Michèle
M
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000962:Antimalarials; D013844:Thiazoles