Auranofin, Et₃PAuCl, and Et₃PAuI Are Highly Cytotoxic on Colorectal Cancer Cells: A Chemical and Biological Study

Abstract

The solution behavior of auranofin, EtPAuCl and EtPAuI, as well as their interactions with hen egg white lysozyme, single strand oligonucleotide, and ds-DNA were comparatively analyzed through NMR spectroscopy, ESI-MS, ethidium bromide displacement, DNA melting and viscometric tests. The cytotoxic effects toward representative colorectal cancer cell lines were found to be strong and similar in the three cases and a good correlation could be established between the cytotoxicity and the ability to inhibit thioredoxin reductase; remarkably, acute toxicity experiments for EtPAuI confirmed that, similarly to auranofin, this drug is well tolerated in a murine model. Overall, a very similar profile emerges for EtPAuI and EtPAuCl, which retain the potent cytotoxic effects of auranofin while showing some peculiar features. These results demonstrate that the presence of the thiosugar moiety is not mandatory for the pharmacological action, suggesting that the tuning of some relevant chemical properties such as lipophilicity could be exploited to improve bioavailability, with no loss of the pharmacological effects.

A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis, Characterization, and Biological Studies

“…The experiments were done according to the procedure detailedi n the Experimental Section. [10] The obtained IC 50 value, falling in the sub-micromolar range, indicates that [Ag(EIA) 2 ]Cl strongly inhibits TrxR, with its inhibitory potencyi ng ood agreement with its cytotoxic effects towardt he SH-SY5Y cancer cell line.…”

“…We analyzed the incubated solutions through a well‐established protocol relying on high‐resolution mass spectrometry (HRMS) . Indeed, binding and interaction with non‐genomic targets such as proteins is recognized to play a key role for the activity of silver and gold carbene complexes . In contrast to expectations, no evidence of adduct formation was detected, even for long incubation times (72 h, see Supporting Information for spectra).…”

Auranofin and its Analogues Show Potent Antimicrobial Activity against Multidrug‐Resistant Pathogens: Structure–Activity Relationships

“…For gold-based complexes the panel includes, as well as AF,t hree gold complexes of general formula [Au(PEt 3 )X] where Xi sahalide ligand;t hese latter compounds are known AF analoguesi nw hich the thiosugar ligand is replaced by chlorido, bromido or iodido ligand. [13] The cationic diphosphino gold(I) and the anionic dicyanoaurate(I)c omplexes, prepared according to reported procedures,w ere also included in the panel of test compounds (see the Experimental Section and Supporting Information for detailso nt heir synthesis, CHN analysis, NMR and UV/Vis spectroscopic characterization). [14] Careful analysis of the obtained resultsp rovides valuable insight on structure-activity relationships.…”

Synthesis, characterization and DNA interactions of [Pt3(TPymT)Cl3], the trinuclear platinum(II) complex of the TPymT ligand

“…To shed further light on the occurring interactions we performed ESI-MS experiments after incubation of the study complex with a simple model of single strand DNA i.e. the dodecameric GG rich oligonucleotide CTACGGTTTCAC (ODN), according to the protocol developed in our laboratory [24][25][26][27][28][29]. In principle, by this approach, it is possible to describe the reaction pattern leading to metallodrug binding to the biomolecular model.…”