Hederagenin as a triterpene template for the development of new antitumor compounds

Diego Rodríguez-Hernández; Antonio J Demuner; Luiz C A Barbosa; René Csuk; Lucie Heller

doi:10.1016/j.ejmech.2015.10.006

Hederagenin as a triterpene template for the development of new antitumor compounds

Eur J Med Chem. 2015 Nov 13:105:57-62. doi: 10.1016/j.ejmech.2015.10.006. Epub 2015 Oct 9.

Authors

Diego Rodríguez-Hernández¹, Antonio J Demuner², Luiz C A Barbosa³, René Csuk⁴, Lucie Heller⁵

Affiliations

¹ Department of Chemistry, Universidade Federal de Viçosa, Av. P. H. Rolfs, s/n, CEP 36570-900, Viçosa, MG, Brazil; Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Campus Pampulha, CEP 31270-901, Belo Horizonte, MG, Brazil.
² Department of Chemistry, Universidade Federal de Viçosa, Av. P. H. Rolfs, s/n, CEP 36570-900, Viçosa, MG, Brazil.
³ Department of Chemistry, Universidade Federal de Viçosa, Av. P. H. Rolfs, s/n, CEP 36570-900, Viçosa, MG, Brazil; Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Campus Pampulha, CEP 31270-901, Belo Horizonte, MG, Brazil. Electronic address: [email protected].
⁴ Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120, Halle (Saale), Germany. Electronic address: [email protected].
⁵ Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120, Halle (Saale), Germany.

PMID: 26476750
DOI: 10.1016/j.ejmech.2015.10.006

Abstract

In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. Although most of the compounds displayed moderate to high levels of cytotoxic activity they were all more potent than the natural product He. The most active compounds had either an ethylpyrimidinyl (27) or an ethylpyrrolidinyl (28) substituent, with EC50 in the range of 1.1-6.5 μM for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He.

Keywords: Folk medicinal plant; Hederagenin derivatives; Pentacyclic triterpenes; SRB assay; Sapindus saponaria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Oleanolic Acid / analogs & derivatives*
Oleanolic Acid / chemical synthesis
Oleanolic Acid / chemistry
Oleanolic Acid / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Oleanolic Acid
hederagenin