Binuclear chloro-bridged palladated and platinated complexes derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxicity against cisplatin resistant tumor cell lines.
Two novel dimeric chloro-bridged complexes [Pd (p-is. TSCN) (mu-Cl)]2, 2, and [Pt (p-is. TSCN)(mu-Cl)]2, 3, where p-is. TSCN = p-isopropylbenzaldehyde thiosemicarbazone, 1, have been synthesized and characterized by IR and NMR spectroscopy. The in vitro antitumor activity shown by both compounds against several human and murine cell lines sensitive and resistant to the clinically-used drug cisplatin (cis-DDP) suggests that compounds 2 and 3 may be endowed with important anticancer properties. Thus, compounds 2 and 3 not only show IC50 values in the microM range as cis-DDP but also display cytotoxic activity in tumor cell lines resistant to this drug. The analysis of the interaction of these binuclear p-is. TSCN compounds with DNA secondary and tertiary structures indicate that they form DNA interhelical cross-links, a biochemical property that may be involved in their mechanism of action.
Quiroga
A G
AG
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Pérez
J M
JM
López-Solera
I
I
Montero
E I
EI
Masaguer
J R
JR
Alonso
C
C
Navarro-Ranninger
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004278:DNA, Superhelical / Q000737:chemistry / Q000187:drug effects; D019281:Dimerization; D004351:Drug Resistance; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004278:DNA, Superhelical; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; C113522:bis(dichloro(4-isopropylbenzaldehyde thiosemicarbazone)palladium(II)); C113523:bis(dichloro(4-isopropylbenzaldehyde-thiosemicarbazone)platinum(II)); D002945:Cisplatin