Synthesis of rocaglamide hydroxamates and related compounds as eukaryotic translation inhibitors: synthetic and biological studies
Journal of medicinal chemistry, 2012•ACS Publications
The rocaglates/rocaglamides are a class of natural products known to display potent
anticancer activity. One such derivative, silvestrol, has shown activity comparable to taxol in
certain settings. Here, we report the synthesis of various rocaglamide analogues and
identification of a hydroxamate derivative (−)-9 having activity similar to silvestrol in vitro and
ex vivo for inhibition of protein synthesis. We also show that (−)-9 synergizes with
doxorubicin in vivo to reduce Eμ-Myc driven lymphomas.
anticancer activity. One such derivative, silvestrol, has shown activity comparable to taxol in
certain settings. Here, we report the synthesis of various rocaglamide analogues and
identification of a hydroxamate derivative (−)-9 having activity similar to silvestrol in vitro and
ex vivo for inhibition of protein synthesis. We also show that (−)-9 synergizes with
doxorubicin in vivo to reduce Eμ-Myc driven lymphomas.
The rocaglates/rocaglamides are a class of natural products known to display potent anticancer activity. One such derivative, silvestrol, has shown activity comparable to taxol in certain settings. Here, we report the synthesis of various rocaglamide analogues and identification of a hydroxamate derivative (−)-9 having activity similar to silvestrol in vitro and ex vivo for inhibition of protein synthesis. We also show that (−)-9 synergizes with doxorubicin in vivo to reduce Eμ-Myc driven lymphomas.
ACS Publications