| Summary: | 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 <b>1</b>), chlorotrimethylphosphine Au(I) (<b>2</b>), 1,3-bis(2,6-diisopropylphenyl) imidazole-2-ylidene Au(I) chloride (<b>3</b>), and chlorotriphenylphosphine Au(I) (<b>4</b>), to affect the sarcoplasmic reticulum (SR) Ca<sup>2+</sup>-ATPase activity. The tested gold compounds strongly inhibit the Ca<sup>2+</sup>-ATPase activity with different effects, being Au(I) compounds <b>2</b> and <b>4</b> the strongest, with half maximal inhibitory concentration (IC<sub>50</sub>) values of 0.8 and 0.9 µM, respectively. For Au(III) compound <b>1</b> and Au(I) compound <b>3</b>, higher IC<sub>50</sub> values are found (4.5 µM and 16.3 µM, respectively). The type of enzymatic inhibition is also different, with gold compounds <b>1</b> and <b>2</b> showing a non-competitive inhibition regarding the native substrate MgATP, whereas for Au compounds <b>3</b> and <b>4</b>, a mixed type of inhibition is observed. Our data reveal, for the first time, Au(I) compounds with powerful inhibitory capacity towards SR Ca<sup>2+</sup>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.
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