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Molecules 2018, 23(8), 2031; https://doi.org/10.3390/molecules23082031

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.
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)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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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