The Ca2+-ATPase Inhibition Potential of Gold(I, III) Compounds

Abstract

The therapeutic applications of gold are well-known for many centuries. The most used gold compounds contain Au(I). Herein, we report, for the first time, the ability of four Au(I) and Au(III) complexes, namely dichloro (2-pyridinecarboxylate) Au(III) (abbreviated as 1), chlorotrimethylphosphine Au(I) (2), 1,3-bis(2,6-diisopropylphenyl) imidazole-2-ylidene Au(I) chloride (3), and chlorotriphenylphosphine Au(I) (4), to affect the sarcoplasmic reticulum (SR) Ca2+-ATPase activity. The tested gold compounds strongly inhibit the Ca2+-ATPase activity with different effects, being Au(I) compounds 2 and 4 the strongest, with half maximal inhibitory concentration (IC50) values of 0.8 and 0.9 µM, respectively. For Au(III) compound 1 and Au(I) compound 3, higher IC50 values are found (4.5 µM and 16.3 µM, respectively). The type of enzymatic inhibition is also different, with gold compounds 1 and 2 showing a non-competitive inhibition regarding the native substrate MgATP, whereas for Au compounds 3 and 4, a mixed type of inhibition is observed. Our data reveal, for the first time, Au(I) compounds with powerful inhibitory capacity towards SR Ca2+ATPase function. These results also show, unprecedently, that Au (III) and Au(I) compounds can act as P-type ATPase inhibitors, unveiling a potential application of these complexes.

Gold Compounds Inhibit the Ca2+-ATPase Activity of Brain PMCA and Human Neuroblastoma SH-SY5Y Cells and Decrease Cell Viability

“…This pump showed the highest affinity for the inhibitor compound 4, followed by compounds 2, 1, and 3. This inhibitory sequence was like that previously observed in the case of SERCA protein [18]. The IC 50 values obtained in our work with PMCA were similar to those reported for SERCA, except for compound 2, which presented a lower inhibitory potency regarding PMCA (IC 50 2.8 µM), in comparison with the value (IC 50 0.8 µM) obtained for SERCA [18].…”

“…This inhibitory sequence was like that previously observed in the case of SERCA protein [18]. The IC 50 values obtained in our work with PMCA were similar to those reported for SERCA, except for compound 2, which presented a lower inhibitory potency regarding PMCA (IC 50 2.8 µM), in comparison with the value (IC 50 0.8 µM) obtained for SERCA [18]. Therefore, these gold(I)-compounds and gold(III)-compounds showed high affinity for PMCA and SERCA.…”

“…Following the addition of the gold compounds, the rates of the reactions in the presence of different inhibitor concentrations were measured within the following 2-3 min. The gold compounds are stable for at least up to 30 min, as previously observed, in the same medium [18]. In fact, compounds were incubated for 30 min with and without the protein, and the inhibitory effects of the ATPase were the same as without any incubation, suggesting that the Au compounds are stable and the effects observed can be attributed to their addition to the medium [18].…”

Vanadium and Melanoma: A Systematic Review

“…The past decades have marked important advances in the traditional view of many roles that metals and their compounds play in biological systems. In fact, metals, inorganic compounds and/or metals-organic frameworks show a diversity of properties that allowed them to present several and distinct biological, environmental and health applications [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Recent insights into metals applications includes for instance, zinc nanoparticles as feed additives showing more efficiency than zinc salts, increasing growth not only in fish [1] but also in plants [2], besides preventing metal contaminants accumulation [2] and normalizing antioxidant biomarkers [1,2].…”

“…Polyoxotungstates (POTs), such as decatungstate (W 10 O 32 4− ), have shown, by photocatalytic activity, to decompose antibiotics namely sulfasalazine and sulfapyridine with different specificities and rates [5]. Besides green biotechnology applications, it was suggested that some POTs hamper melanoma cancer cells growth through inhibition of aquaporin-3 activity [6], whereas others POTs as well as gold compounds showed specific inhibitory activities for P-type ATPases [7,8].…”