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Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A.

ABSTRACT: N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br-, I-, C?C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based proliferation assays against the human colon carcinoma cell line HCT-116wt and the multidrug-resistant human breast carcinoma cell line MCF-7topo. Most complexes showed good cytotoxicity with IC50 values in the low micromolar range, while excellent sub-micromolar activity was observed for 2c, 3a and 3b. Generally, the activity of the ligands studied was as follows: carbene > phosphine > alkyne > halide, with an exception for the highly active iodido derivative 2c.

SUBMITTER: Curran D

PROVIDER: S-EPMC7436326 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A.

Curran Danielle D Müller-Bunz Helge H Bär Sofia I SI Schobert Rainer R Zhu Xiangming X Tacke Matthias M

Molecules (Basel, Switzerland) 20200730 15

N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br-, I-, C≡C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5 ...[more]

PMID: 32751607

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

Project description: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 (3?5), p-mercaptobenzoate derivatives (12?14) and N-acetyl-l-cysteine derivatives (15?17). 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 ?M ± 0.03 ?M. 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 PPh?.

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