New bis-thiazolium analogues as potential antimalarial agents: design, synthesis, and biological evaluation.
Basic Information
ID: ALA2311439
Journal: J Med Chem
Title: New bis-thiazolium analogues as potential antimalarial agents: design, synthesis, and biological evaluation.
Authors: Caldarelli SA, El Fangour S, Wein S, Tran van Ba C, Périgaud C, Pellet A, Vial HJ, Peyrottes S.
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).
CiteXplore: 23289711
DOI: 10.1021/jm3014585
Patent ID: ┄