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 - Janošt'Áková, Anna
AU - Wang, Shudong
AU - Parsons, Simon
AU - Fischer, Peter M.
AU - Zhelev, Nikolai Z.
AU - Hajdúch, Marián
PY - 2003/12/4
Y1 - 2003/12/4
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.
UR - http://www.scopus.com/inward/record.url?scp=10744224623&partnerID=8YFLogxK
U2 - 10.1021/jm020854p
DO - 10.1021/jm020854p
M3 - Article
C2 - 14640549
AN - SCOPUS:10744224623
SN - 0022-2623
VL - 46
SP - 5402
EP - 5415
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 25
ER -
