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ID: ALA1146596

Journal: J Med Chem

Title: New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure-activity relationships.

Authors: Sarek J, Klinot J, Dzubák P, Klinotová E, Nosková V, Krecek V, Korínková G, Thomson JO, Janost'áková A, Wang S, Parsons S, Fischer PM, Zhelev NZ, Hajdúch M.

Abstract: 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.

CiteXplore: 14640549

DOI: 10.1021/jm020854p