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 Janošťáková, Shudong Wang, Simon Parsons, Peter M. Fischer, Nikolai Zhelev, Marián Hajdúch

Research output: Contribution to journal › Article

81 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 - 2003

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Pentacyclic Triterpenes
Neoplasms
Tumor Cell Line
Ketones
Oxygen
Pharmaceutical Preparations
lupane
betulin
In Vitro Techniques
betulinic acid

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Šarek, J., Klinot, J., Džubák, P., Klinotová, E., Nosková, V., Křeček, V., ... Hajdúch, M. (2003). New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure−activity relationships. Journal of Medicinal Chemistry, 46(25), 5402–5415. https://doi.org/10.1021/jm020854p
Šarek, Jan ; Klinot, Jiří ; Džubák, Petr ; Klinotová, Eva ; Nosková, Věra ; Křeček, Václav ; Kořínková, Gabriela ; Thomson, Jean Oliver ; Janošťáková, Anna ; Wang, Shudong ; Parsons, Simon ; Fischer, Peter M. ; Zhelev, Nikolai ; Hajdúch, Marián. / New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure−activity relationships. In: Journal of Medicinal Chemistry. 2003 ; Vol. 46, No. 25. pp. 5402–5415.
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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.",
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Šarek, J, Klinot, J, Džubák, P, Klinotová, E, Nosková, V, Křeček, V, Kořínková, G, Thomson, JO, Janošťáková, A, Wang, S, Parsons, S, Fischer, PM, Zhelev, N & Hajdúch, M 2003, 'New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure−activity relationships', Journal of Medicinal Chemistry, vol. 46, no. 25, pp. 5402–5415. https://doi.org/10.1021/jm020854p

New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure−activity relationships. / Šarek, Jan; Klinot, Jiří; Džubák, Petr; Klinotová, Eva; Nosková, Věra; Křeček, Václav; Kořínková, Gabriela; Thomson, Jean Oliver; Janošťáková, Anna; Wang, Shudong; Parsons, Simon; Fischer, Peter M.; Zhelev, Nikolai; Hajdúch, Marián.

In: Journal of Medicinal Chemistry, Vol. 46, No. 25, 2003, p. 5402–5415.

Research output: Contribution to journal › Article

TY - JOUR

T1 - New lupane derived compounds with pro-apoptotic activity in cancer cells: 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 -

Šarek J, Klinot J, Džubák P, Klinotová E, Nosková V, Křeček V et al. New lupane derived compounds with pro-apoptotic activity in cancer cells: synthesis and structure−activity relationships. Journal of Medicinal Chemistry. 2003;46(25):5402–5415. https://doi.org/10.1021/jm020854p

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