Activity of rat cytosolic thioredoxin reductase is strongly decreased by trans-[bis(2-amino-5- methylthiazole)tetrachlororuthenate(III)]: first report of relevant thioredoxin reductase inhibition for a ruthenium compound.
A novel "Keppler type" ruthenium(III) compound trans-[bis(2-amino 5-methylthiazole)tetrachlororuthenate(III)] 1, of potential interest as an anticancer agent, was designed, synthesized, and characterized. Its interactions with various proteins were analyzed, including the selenoenzyme thioredoxin reductase, an emerging target for anticancer metallodrugs. The selective inhibition of the cytosolic form of this selenoenzyme was documented, this being the first report of significant thioredoxin reductase inhibition by a ruthenium compound.
Mura
Pasquale
P
Institute of Crystallography, Area della Ricerca di Roma 1 (CNR), Via Salaria Km 29,300, Montelibretti, Rome, Italy. pasquale.mura@ic.cnr.it
Camalli
Mercedes
M
Bindoli
Alberto
A
Sorrentino
Francesca
F
Casini
Angela
A
Gabbiani
Chiara
C
Corsini
Maddalena
M
Zanello
Piero
P
Rigobello
Maria Pia
MP
Messori
Luigi
L
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003600:Cytosol / Q000201:enzymology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008928:Mitochondria / Q000201:enzymology; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D054481:Thioredoxin Reductase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054482:Thioredoxin Reductase 2 / Q000037:antagonists & inhibitors / Q000737:chemistry
D000970:Antineoplastic Agents; D007527:Isoenzymes; D009942:Organometallic Compounds; C526806:bis(2-amino-5-methylthiazole)tetrachlororuthenate(III); D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; C516126:Txnrd1 protein, rat