title: Antimalarial cation-dimers synthesized in two steps from an inexpensive starting material, isonicotinic acid.
abstract: Malaria is one of the three major serious infectious diseases in the world. As the area affected by malaria includes a large proportion of developing countries, there is a need for new antimalarials that can be synthesized and supplied inexpensively. To generate low-cost antimalarials, the MAP series 6-10, bis-cation dimers, synthesized by amidating the carboxyl group of isonicotinic acid (11) with various amines and by cationizing the nitrogen atoms of the pyridine ring with the corresponding alkyl bromides, were designed. This design enabled expansion of the structural variations of bis-cation-type antimalarial compounds. The compounds bearing alkyl or phenyl groups in the amide moieties showed remarkable antimalarial activities in vitro. Moreover, 1,1'-(1,12-dodecanediyl)bis[4-[(buthylamino)carbonyl]pyridinium bromide], MAP-412 (6 d), exhibited a potent antimalarial activity (ED(50)=8.2 mg kg(-1)). Being prepared at low cost, our bis-cation-type antimalarial compounds may be useful as lead compounds for inexpensive antimalarials.
authors.affiliation: Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 1-1-1, Tsushima-Naka, Okayama 700-8530, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Motoshima
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hiwasa
authors.forename: Mai
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Kanji
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kakuta
authors.forename: Kenji
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry; D002412:Cations; D019281:Dimerization; D007539:Isonicotinic Acids / Q000737:chemistry* / Q000191:economics
chemical_list: D000962:Antimalarials; D002412:Cations; D007539:Isonicotinic Acids