Novel hederagenin-triazolyl derivatives as potential anti-cancer agents

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

doi:10.1016/j.ejmech.2016.03.018

Novel hederagenin-triazolyl derivatives as potential anti-cancer agents

Eur J Med Chem. 2016 Jun 10:115:257-67. doi: 10.1016/j.ejmech.2016.03.018. Epub 2016 Mar 9.

Authors

Diego Rodríguez-Hernández¹, Antonio J Demuner², Luiz C A Barbosa³, Lucie Heller⁴, René Csuk⁵

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.
⁵ Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany. Electronic address: [email protected].

PMID: 27017553
DOI: 10.1016/j.ejmech.2016.03.018

Abstract

A series of novel aryl-1H-1,2,3-triazol-4-yl methylester and amide derivatives of the natural product hederagenin was synthesized aiming to develop new antitumor agents, using Huisgen 1,3-dipolar cycloaddition reactions, with yields between 35% and 95%. The structures of all derivatives (2-31) were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic data. The cytotoxic activities of all compounds were screened against a panel of six human cancer cell lines using SRB assay. It was found that most of the compounds displayed higher levels of antitumor activities as compared to parent hederagenin. Compounds 4, 8 and 15 were the most potent against all human cancer cell lines. Furthermore, compound 11 was the most cytotoxic against cell HT29 showing EC50 = 1.6 μM and a selectivity index of 5.4.

Keywords: Hederagenin derivatives; Huisgen 1,3-dipolar cycloaddition; SRB assay; Sapindus saponaria.

Publication types

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

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Oleanolic Acid / analogs & derivatives*
Oleanolic Acid / chemistry
Triazoles / chemistry*

Substances

Antineoplastic Agents
Triazoles
Oleanolic Acid
hederagenin