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Open AccessFeature PaperArticle

Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A

1
School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
2
Organic Chemistry Laboratory, University of Bayreuth, Universitätsstr. 30, 95440 Bayreuth, Germany
3
Irish Centre of High-End Computing, Grand Canal Quay, Dublin 2, Ireland
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(8), 2031; https://doi.org/10.3390/molecules23082031
Received: 3 August 2018 / Revised: 7 August 2018 / Accepted: 13 August 2018 / Published: 14 August 2018
(This article belongs to the Special Issue Metal Complexes of Biological Ligands)
Ten novel N-heterocyclic carbene gold(I) complexes derived from lepidiline A (1,3-dibenzyl-4,5-dimethylimidazolium chloride) are reported here with full characterisation and biological testing. (1,3-Dibenzyl-4,5-diphenylimidazol-2-ylidene)gold(I) chloride (NHC*-AuCl) (1) was modified by substituting the chloride for the following: cyanide (2), dithiocarbamates (35), p-mercaptobenzoate derivatives (1214) and N-acetyl-l-cysteine derivatives (1517). All complexes were synthesised in good yields of 57–78%. Complexes 2, 12, 13, and 14 were further characterised by X-ray crystallography. Initial evaluation of the biological activity was conducted on all ten complexes against the multidrug resistant MCF-7topo breast cancer, HCT-116wt, and p53 knockout mutant HCT-116−/− colon carcinoma cell lines. Across the three cell lines tested, mainly single-digit micromolar IC50 values were observed. Nanomolar activity was exhibited on the MCF-7topo cell line with 3 displaying an IC50 of 0.28 μM ± 0.03 μM. Complexes incorporating a Au–S bond resulted in higher cytotoxic activity when compared to complexes 1 and 2. Theoretical calculations, carried out at the MN15/6–311++G(2df,p) computational level, show that NHC* is the more favourable ligand for Au(I)-Cl when compared to PPh3. View Full-Text
Keywords: lepidiline A; N-heterocyclic carbene; gold anticancer drug; TrxR inhibition; MTT cytotoxicity assay; DFT calculations lepidiline A; N-heterocyclic carbene; gold anticancer drug; TrxR inhibition; MTT cytotoxicity assay; DFT calculations
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Curran, D.; Dada, O.; Müller-Bunz, H.; Rothemund, M.; Sánchez-Sanz, G.; Schobert, R.; Zhu, X.; Tacke, M. Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from Lepidiline A. Molecules 2018, 23, 2031.

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