Biological activities of pyrenyl-derived thiosemicarbazone half-sandwich complexes

Pyrenyl-derived thiosemicarbazone half-sandwich complexes of the types [(eta(6)-p-MeC6H4Pri)Ru(L-n)Cl](+) and [(eta(5)-C5Me5)M(L-n)Cl](+) (M = Rh, Ir; L-1 = pyrenecarboxaldehyde-3-thiosemicarbazone, L-2 = pyrenecarboxaldehyde-4-methyl-3-thiosemicarbazone, L-3 = pyrenecarboxaldehyde-4-phenyl-3-thiosemicarbazone) were synthesized and isolated as their chloride salts by reacting in THF the dinuclear complexes [(eta(6)-P-MeC6H4Pri)(2)Ru-2(mu-Cl)(2)Cl-2] and [(eta(5)-C5Me5)(2)M-2(mu-Cl)(2)Cl-2] with the corresponding ligand. All complexes were isolated in good yields and were fully characterized by spectroscopic methods, including single-crystal X-ray structure analyses of the ruthenium complex [(eta(6)-p-MeC6H4Pri) Ru(L1)Cl]Cl and the rhodium derivative [(eta(5)-C5Me5)Rh(L-2)Cl]Cl. The complexes were found to have IC50 values in the micromolar range against cancer cells (A-549, DU-145, HeLa, MCF-7), with a lower cytotoxicity in the noncancerous human HEK-293 embryonic kidney cells. The best two candidates, the rhodium derivatives [(eta(5)-C5Me5)Rh(L-1)Cl]Cl and [(eta(5)-C5Me5)Rh(L-3)Cl]Cl, show anticancer activities comparable to doxorubicin. These two complexes were further evaluated, showing an inhibition of the cell cycle at the G2/M and subG1 stages. (C) 2015 Elsevier B.V. All rights reserved.