TY - JOUR
T1 - New lupane derived compounds with pro-apoptotic activity in cancer cells
T2 - synthesis and structure−activity relationships
AU - Šarek, Jan
AU - Klinot, Jiří
AU - Džubák, Petr
AU - Klinotová, Eva
AU - Nosková, Věra
AU - Křeček, Václav
AU - Kořínková, Gabriela
AU - Thomson, Jean Oliver
AU - Janošťáková, Anna
AU - Wang, Shudong
AU - Parsons, Simon
AU - Fischer, Peter M.
AU - Zhelev, Nikolai
AU - Hajdúch, Marián
PY - 2003
Y1 - 2003
N2 - Cellular screening of various synthetic triterpenoid compounds formally derived from lupane has identified a number of analogues as potential anticancer drug candidates. Here we describe the synthesis and structure−activity relationships of betulin and betulinic acid derivatives containing an E-ring modified with different oxygen functions. Thus compounds containing the lup-18-en-21-one, lup-18-ene-21,22-dione, 18,19-secolupane, and the highly oxygenated 18,19-secolupane systems, as well as des-E-lupane derivatives, were prepared from the readily available natural pentacyclic triterpene betulin using oxidative procedures. These compounds were named betulinines. We demonstrate that only selected compounds, particularly those containing a lupane E-ring-derived unsaturated ketone or diketone function, possessed in vitro cytotoxic activity against tumor cell lines, suggesting a structure−activity relationship.
AB - Cellular screening of various synthetic triterpenoid compounds formally derived from lupane has identified a number of analogues as potential anticancer drug candidates. Here we describe the synthesis and structure−activity relationships of betulin and betulinic acid derivatives containing an E-ring modified with different oxygen functions. Thus compounds containing the lup-18-en-21-one, lup-18-ene-21,22-dione, 18,19-secolupane, and the highly oxygenated 18,19-secolupane systems, as well as des-E-lupane derivatives, were prepared from the readily available natural pentacyclic triterpene betulin using oxidative procedures. These compounds were named betulinines. We demonstrate that only selected compounds, particularly those containing a lupane E-ring-derived unsaturated ketone or diketone function, possessed in vitro cytotoxic activity against tumor cell lines, suggesting a structure−activity relationship.
U2 - 10.1021/jm020854p
DO - 10.1021/jm020854p
M3 - Article
VL - 46
SP - 5402
EP - 5415
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 25
ER -