New Lupane Derived Compounds with Pro-Apoptotic Activity in Cancer Cells: Synthesis and Structure-Activity Relationships

Jan Šarek, Jiří Klinot, Petr Džubák, Eva Klinotová, Věra Nosková, Václav Křeček, Gabriela Kořínková, Jean Oliver Thomson, Anna Janošt'Áková, Shudong Wang, Simon Parsons, Peter M. Fischer, Nikolai Z. Zhelev, Marián Hajdúch

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5402-5415
Number of pages14
JournalJournal of Medicinal Chemistry
Volume46
Issue number25
DOIs
Publication statusPublished - 4 Dec 2003

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