Binuclear chloro-bridged palladated and platinated complexes derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxicity against cisplatin resistant tumor cell lines

• Published in: Journal of inorganic biochemistry Vol. 69; no. 4; pp. 275 - 281
• Main Authors: Quiroga, Adoración G, M. Pérez, José, López-Solera, Isabel, Montero, Eva I, Masaguer, José R, Alonso, Carlos, Navarro-Ranninger, Carmen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-1998
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cisplatin; Cisplatin - pharmacology; Cross-Linking Reagents - chemical synthesis; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - pharmacology; Cytotoxicity, DNA cross-links; Dimerization; DNA, Superhelical - chemistry; DNA, Superhelical - drug effects; Drug Resistance; Humans; In Vitro Techniques; Magnetic Resonance Spectroscopy; Mice; Nucleic Acid Conformation; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Organoplatinum Compounds - chemical synthesis; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Thiosemicarbazone; Tumor Cells, Cultured; MTT, 3-[4,5-dymethylthiazol-2-y1]-2,5diphenyltetrazolium bromide; Thiosemicarbazone; cis-diamminedichloroplatinum (II); p-is.TSCN, p-isopropylbenzaldehyde thiosemicarbazone; EDTA, ethylenediaminetetracetate; Cytotoxicity, DNA cross-links; Cisplatin; cis-DDP; Tris, tris-hydroxymethylaminomethane
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/S0162-0134(98)00003-8

Two novel dimeric chloro-bridged complexes [Pd (
p-is.TSCN) (μ-Cl)]
2,
2, and [Pt (
p-is.TSCN)(μ-C1)]
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 IC
50 values in the μM 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.