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

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 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.