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

doi:10.1021/jm020854p

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 journal › Article › peer-review

94 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 language	English
Pages (from-to)	5402-5415
Number of pages	14
Journal	Journal of Medicinal Chemistry
Volume	46
Issue number	25
DOIs	https://doi.org/10.1021/jm020854p
Publication status	Published - 4 Dec 2003

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm020854p

Cite this

Šarek, J., Klinot, J., Džubák, P., Klinotová, E., Nosková, V., Křeček, V., Kořínková, G., Thomson, J. O., Janošt'Áková, A., Wang, S., Parsons, S., Fischer, P. M., Zhelev, N. Z., & 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

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

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.",

author = "Jan {\v S}arek and Ji{\v r}{\'i} Klinot and Petr D{\v z}ub{\'a}k and Eva Klinotov{\'a} and V{\v e}ra Noskov{\'a} and V{\'a}clav K{\v r}e{\v c}ek and Gabriela Ko{\v r}{\'i}nkov{\'a} and Thomson, \{Jean Oliver\} and Anna Jano{\v s}t'{\'A}kov{\'a} and Shudong Wang and Simon Parsons and Fischer, \{Peter M.\} and Zhelev, \{Nikolai Z.\} and Mari{\'a}n Hajd{\'u}ch",

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Šarek, J, Klinot, J, Džubák, P, Klinotová, E, Nosková, V, Křeček, V, Kořínková, G, Thomson, JO, Janošt'Áková, A, Wang, S, Parsons, S, Fischer, PM, Zhelev, NZ & 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

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 - https://www.scopus.com/pages/publications/10744224623

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DO - 10.1021/jm020854p

M3 - Article

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SN - 0022-2623

VL - 46

SP - 5402

EP - 5415

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 25

ER -

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

Abstract

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