Improved Antiproliferative Activity and Fluorescence of a Dinuclear Gold(I) Bisimidazolylidene Complex via Anthracene‐Modification

Abstract

A straightforward modification route to obtain mono‐ and di‐substituted anthroyl ester bridge functionalized dinuclear Au(I) bis‐N‐heterocyclic carbene complexes is presented. The functionalization can be achieved starting from a hydroxyl‐functionalized ligand precursor followed by transmetallation of the corresponding Ag complex or via esterification of the hydroxyl‐functionalized gold complex. The compounds are characterized by NMR‐spectroscopy, ESI‐MS, elemental analysis and SC‐XRD. The mono‐ester Au complex shows quantum yields around 18%. In contrast, the corresponding syn‐di‐ester Au complex, exhibits significantly lower quantum yields of around 8%. Due to insufficient water solubility of the di‐ester, only the mono‐ester complex has been tested regarding its antiproliferative activity against HeLa‐ (cervix) and MCF‐7‐ (breast) cancer cell lines and a healthy fibroblast cell line (V79). IC50 values of 7.26 μM in the HeLa cell line and 7.92 μM in the MCF‐7 cell line along with selectivity indices of 8.8 (HeLa) and 8.0 (MCF‐7) are obtained. These selectivity indices are significantly higher than those obtained for the reference drugs cisplatin or auranofin.

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…It has better selectivity than the reference complexes cisplatin and auranofin. 162 In 2020, Luengo et al reported a series of neutral and cationic heterotrimetallic Re(I)-Au(I) complexes 221a-c. Luminescent studies showed that all the complexes displayed a broad emission band centered between 565 nm and 680 nm. The ancillary ligands were used to modulate the luminescent and/or bioactivity of the metal probes in order to allow the detection of the precise moment of interaction with the biological target.…”

“…It has better selectivity than the reference complexes cisplatin and auranofin. 162 In 2020, Luengo et al reported a series of neutral and cationic heterotrimetallic Re( i )–Au( i ) complexes 221a – c . Luminescent studies showed that all the complexes displayed a broad emission band centered between 565 nm and 680 nm.…”

Exploiting click-chemistry: backbone post-functionalisation of homoleptic gold(i) 1,2,3-triazole-5-ylidene complexes

“…26 Post-functionalisation strategies typically include biologically native functional groups. 22,23,33 While these have been reported for attaching small molecules, 17,19,22,23,33,34 we only found one example where the post-conjugation to an antibody was facilitated, however here efficacy of the resulting ADCs was hampered due to their low cytotoxicity. 10 The strain promoted azide alkyne cycloaddition (SPAAC) was established by Bertozzi et al as a reliable, selective and versatile technique for the conjugation of biomolecules and was awarded with the Nobel prize in chemistry in 2022.…”

“…15,16 To further enhance the selectivity towards cancer cells, several examples of Au( i ) NHC im complexes suitable for post-modification have been reported. They bear inter alia hydroxyl, 17–19 activated ester, 10,20 azide 21 and carboxylic acid 22,23 functional groups, which are available for further bioconjugation. The azide–alkyne cycloaddition (AAC) reaction has proven successful on both pre- and post-functionalisation of Au( i ) NHC im -complexes.…”

Reactivity of antitumor coinage metal-based N-heterocyclic carbene complexes with cysteine and selenocysteine protein sites

“…Indeed, ([Ag(EIA)2]Cl was able to bind the C-terminal dodecapeptide hTrxR(488-499) reproducing the active site of thioredoxin reductase and inhibiting the enzymatic activity. Furthermore, anthracene functionalized silver carbenes were found to inhibit TrxR [35] and their use includes the possibility of imaging upon administration to cells; yet their DNA binding has only been marginally explored [36]. Moreover, it was noted that silver compounds are capable to targeting non-genomic targets such as mitochondria and proteins [30,31,37,38].…”