BioMetals

, Volume 27, Issue 1, pp 183–194

Gold complexes with benzimidazole derivatives: synthesis, characterization and biological studies

  • Vinicius Zamprogno Mota
  • Gustavo Senra Gonçalves de Carvalho
  • Adilson David da Silva
  • Luiz Antônio Sodré Costa
  • Patrícia de Almeida Machado
  • Elaine Soares Coimbra
  • Carmen Veríssima Ferreira
  • Silvia Mika Shishido
  • Alexandre Cuin
Article

DOI: 10.1007/s10534-014-9703-1

Cite this article as:
Mota, V.Z., de Carvalho, G.S.G., da Silva, A.D. et al. Biometals (2014) 27: 183. doi:10.1007/s10534-014-9703-1

Abstract

Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG–DTA) analyses, and FT-IR and UV–Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC50 values below 5.7 μM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.

Keywords

Benzimidazole Gold Leishmania Cancer Cytotoxicity 

Abbreviations

NMR

Nuclear magnetic resonance

T

Triplet

D

Duplet

TG/DTA

Thermogravimetric/differencial thermal analysis

UV–Vis

Ultraviolet–Visible spectroscopy

Lig1

1-Benzyl-2-phenyl-1H-benzimidazole

Lig2

1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzimidazole

DMSO

Dimethylsulfoxide

CDCl3

Chloroform-d

DFT

Density functional theory

TD

Time dependent method

Ab initio

From Latin, means “from the beginning”

ECP

Effective core potential

SDD

Stuttgart/Dresden ECP

B3LYP

Becke 3 parameter hybrid functional with non-local Lee–Yang–Parr expression

IEFPCM

Integral equation formalism on polarizable continuum model

HOMO/LUMO

Highest occupied/lowest unoccupied molecular orbital

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

DMEM

Dulbecco’s modified eagle’s medium

FBS

Fetal bovine serum

Balb/c 3T3

Mouse embryonic fibroblast

SK-Mel 103

Human melanoma cells

Panc-1

Human pancreatic carcinoma

BHI

Brain Heart Infusion

LPS

Lipopolysaccharide

Supplementary material

10534_2014_9703_MOESM1_ESM.doc (269 kb)
(DOC 269 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Vinicius Zamprogno Mota
    • 1
  • Gustavo Senra Gonçalves de Carvalho
    • 2
  • Adilson David da Silva
    • 2
  • Luiz Antônio Sodré Costa
    • 3
  • Patrícia de Almeida Machado
    • 4
  • Elaine Soares Coimbra
    • 4
  • Carmen Veríssima Ferreira
    • 5
  • Silvia Mika Shishido
    • 5
  • Alexandre Cuin
    • 1
  1. 1.LQBin, Laboratório de Química BioInorgânica, Departamento de Química, Instituto de Ciências ExatasUniversidade Federal de Juiz de ForaJuiz de ForaBrazil
  2. 2.Departamento de Química, Instituto de Ciências ExatasUniversidade Federal de Juiz de ForaJuiz de ForaBrazil
  3. 3.NEQC, Núcleo de Estudos em Química Computacional, Departamento de Química, Instituto de Ciências ExatasUniversidade Federal de Juiz de ForaJuiz de ForaBrazil
  4. 4.Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências BiológicasUniversidade Federal de Juiz de ForaJuiz de ForaBrazil
  5. 5.Laboratório de Bioensaios e Transdução de Sinal, Departamento de Bioquímica, Instituto de BiologiaUniversidade Estadual de CampinasCampinasBrazil

Personalised recommendations