title: Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors.
abstract: Aiming to develop selective anticancer drugs, we designed and synthesized three disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1 displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast cancer cells. The activity of 1 was significantly reduced by free folic acid, suggesting that cellular uptake of 1 is mediated by FR.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Hisakawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itoh
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kawahata
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
mesh_terms: D002352:Carrier Proteins / Q000187:drug effects*; D045744:Cell Line, Tumor; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D058973:Folate Receptors, GPI-Anchored; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D058973:Folate Receptors, GPI-Anchored; D056572:Histone Deacetylase Inhibitors; D011355:Prodrugs; D011956:Receptors, Cell Surface; D013438:Sulfhydryl Compounds