Structure-activity relationships of quassinoids for eukaryotic protein synthesis.
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.
Fukamiya
Narihiko
N
Faculty of Integrated Arts and Sciences, Hiroshima University, Kagamiyama 1-7-1, Higashi, Hiroshima 739-8521, Japan.
Lee
Kuo-Hsiung
KH
Muhammad
Ilias
I
Murakami
Chihiro
C
Okano
Masayohis
M
Harvey
Isabelle
I
Pelletier
Jerry
J
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
D011500:Protein Synthesis Inhibitors; D036702:Quassins