TY - JOUR
T1 - The ca2+-atpase inhibition potential of gold(I, iii) compounds
AU - Fonseca, Custódia
AU - Fraqueza, Gil
AU - Carabineiro, Sónia A. C.
AU - Aureliano, Manuel
N1 - Fundacao para a Ciencia e a Tecnologia (FCT) project UIDB/04326/2020 and Associate Laboratory for Green Chemistry-LAQV, financed by national funds from FCT/MCTES (UIDB/50006/2020).
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - Anticancer
KW - Ca-ATPase
KW - Gold(I, III) compounds
KW - P-type ATPases inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85094562602&partnerID=8YFLogxK
U2 - 10.3390/inorganics8090049
DO - 10.3390/inorganics8090049
M3 - Article
AN - SCOPUS:85094562602
VL - 8
SP - 1
EP - 11
JO - Inorganics
JF - Inorganics
SN - 2304-6740
IS - 9
M1 - 49
ER -