title: New bis-thiazolium analogues as potential antimalarial agents: design, synthesis, and biological evaluation.
abstract: Bis-thiazolium salts are able to inhibit phosphatidylcholine biosynthesis in  Plasmodium  and to block parasite proliferation in the low nanomolar range. However, due to their physicochemical properties (i.e., permanent cationic charges, the flexibility, and lipophilic character of the alkyl chain), the oral bioavailability of these compounds is low. New series of bis-thiazolium-based drugs have been designed to overcome this drawback. They feature linker rigidification via the introduction of aromatic rings and/or a decrease in the overall lipophilicity through the introduction of heteroatoms. On the basis of the structure-activity relationships, a few of the promising compounds (9, 10, and 11) were found to exhibit potent antimalarial in vitro and in vivo activities (EC(50) < 10 nM and ED(50) ip < 0.7 mg/kg).
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1&2, Université Montpellier 2, cc 1705, place E. Bataillon, 34095 Montpellier, France.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Caldarelli
authors.forename: Siham
authors.initials: S
authors.lastname: El Fangour
authors.forename: Sharon
authors.initials: S
authors.lastname: Wein
authors.forename: Christophe
authors.initials: C
authors.lastname: Tran van Ba
authors.forename: Christian
authors.initials: C
authors.lastname: Périgaud
authors.forename: Alain
authors.initials: A
authors.lastname: Pellet
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Vial
authors.forename: Suzanne
authors.initials: S
authors.lastname: Peyrottes
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D013844:Thiazoles