title: Borrelidin analogues with antimalarial activity: design, synthesis and biological evaluation against Plasmodium falciparum parasites.
abstract: Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC50 value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH2SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells.
authors.affiliation: The Kitasato Institute and Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sugawara
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Hirose
authors.forename: Aki
authors.initials: A
authors.lastname: Ishiyama
authors.forename: Masato
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Otoguro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D005233:Fatty Alcohols; C005066:borrelidin