title: Structure-activity relationships of quassinoids for eukaryotic protein synthesis.
abstract: The effect of 63 quassinoids on eukaryotic protein synthesis has been investigated. Seventeen of the tested compounds showed potent in vitro activity, with IC50s below 2 microM for inhibition in Krebs ascites translation extracts. Sixteen of these quassinoids were also potent inhibitors of in vivo protein synthesis when exposed to Hela cells for 1 h. Our results led to the following structure-activity relationships for quassinoids regarding translation inhibition. Activity is influenced by (i) the nature of the C-15 side chain, (ii) the nature of A ring modifications, (iii) the presence or absence of a sugar moiety, and (iv) the presence of an epoxymethano bridge.
authors.affiliation: Faculty of Integrated Arts and Sciences, Hiroshima University, Kagamiyama 1-7-1, Higashi, Hiroshima 739-8521, Japan.
authors.forename: Narihiko
authors.initials: N
authors.lastname: Fukamiya
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Ilias
authors.initials: I
authors.lastname: Muhammad
authors.forename: Chihiro
authors.initials: C
authors.lastname: Murakami
authors.forename: Masayohis
authors.initials: M
authors.lastname: Okano
authors.forename: Isabelle
authors.initials: I
authors.lastname: Harvey
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D000818:Animals; D005057:Eukaryotic Cells / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D036702:Quassins / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011500:Protein Synthesis Inhibitors; D036702:Quassins