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Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Structure-activity relationships of quassinoids for eukaryotic protein synthesis
Narihiko Fukamiya1, Kuo-Hsiung Lee, Ilias Muhammad
1Faculty of Integrated Arts and Sciences, Hiroshima University, Kagamiyama 1-7-1, Higashi, Hiroshima 739-8521, Japan.
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.
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