New lupane derived compounds with pro-apoptotic activity in cancer cells: Synthesis and structure - Activity relationships

J Sarek, J Klinot, P Dzubak, E Klinotiva, V Noskova, V Krecek, G Korinkova, J P Thomson, A Janost'akova, S D Wang, S Parsons, P M Fischer, N Z Zhelev, M Hajduch

Research output: Contribution to journalArticlepeer-review

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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