Gold(i) complexes of water-soluble diphos-type ligands: Synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition

Abstract

Gold(I) complexes of imidazole and thiazole-based diphos type ligands were prepared and their potential as chemotherapeutics investigated. Depending on the ligands employed and the reaction conditions complexes [L(AuCl)(2)] and [L(2)Au]X (X = Cl, PF(6)) are obtained. The ligands used are diphosphanes with azoyl substituents R(2)P(CH(2))(2)PR(2) {R = 1-methylimidazol-2-yl (1), 1-methylbenzimidazol-2-yl (4), thiazol-2-yl (5) and benzthiazol-2-yl (6)} as well as the novel ligands RPhP(CH(2))(2)PRPh {R = 1-methylimidazol-2-yl (3)} and R(2)P(CH(2))(3)PR(2) {R = 1-methylimidazol-2-yl (2)}. The cytotoxic activity of the complexes was assessed against three human cancer cell lines and a rat hepatoma cell line and correlated to the lipophilicity of the compounds. The tetrahedral gold complexes [(3)(2)Au]PF(6) and [(5)(2)Au]PF(6) with intermediate lipophilicity (logD(7.4) = 0.21 and 0.25) showed significant cytotoxic activity in different cell lines. Both compounds induce apoptosis and inhibit the enzymes thioredoxin reductase and glutathione reductase.

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

“…Distribution Coefficient (log D 7.4 ): The n ‐octanol/water coefficients of the complexes were determined as previously reported using the shake‐flask method. Buffered distilled water (100 mL, phosphate buffer [PO 4 3– ] = 10 µ m , [NaCl] = 0.15 m , pH 7.4) and n ‐octanol (100 mL) were shaken together for 72 h to allow saturation of both phases.…”

Metallodrug induced apoptotic cell death and survival attempts are characterizable by Raman spectroscopy

“…6 During the early phases of metallodrug research, it was found that derivatives containing the linear P-Au-S structure found in auranofin (a known rheumatoid arthritis drug) had potential for treating cancer. 5 Successful cancer treatments are expected to selectively kill diseased cells only and the cytotoxic effects of the drugs are routinely monitored by conventional biochemical assays such as 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assays, 7 microscopy, flow cytometric techniques, 8 and real time cell electronic sensing (RT-CES). 9 The disadvantages of some of these techniques are that expensive reagents are needed and specialised instruments to measure absorbance, impedance, fluorescence, or luminescence of labelled biosensors.…”

Synthesis, structural and spectral properties of Au complexes: luminescence properties and their non‐covalent DNA binding studies

“…In the literature, gold complexes have been studied for potential antitumor properties, and it was shown that complexes of the type [(R 3 P)Au(thiolate)] exhibit antitumor properties; furthermore, gold(I) phosphane derivatives or gold(I) complexes of bisphosphanes have also shown significant activity in murine tumor . In addition, although gold(I) complexes like [(dppe) 2 Au] + (dppe = 1,2‐bis‐(diphenylphosphino)ethane) exhibit promising cytotoxicity in preclinical studies, they produce other severe adverse effects (cardiac, hepatic and vascular toxicity) .…”