Synthesis, characterization, and in vitro antiproliferative activity of [salophene]platinum(II) complexes.
A series of methoxy- and fluorine-substituted [salophene]platinum(II) complexes (salophene=N,N'-bis(salicylidene)-1,2-phenylenediamine) were synthesized and characterized by (1) H NMR spectroscopy and mass spectrometry. The structure was confirmed on the example of [5-OCH3 -salophene]platinum(II) (4-Pt) by crystal structure analysis. The cytotoxicity of all complexes against MCF-7 cells showed strong dependence on the kind of substituent and its position on the salicylidene moiety, whereas 1-Pt (H), 3-Pt (4-OCH3 ), and 6-Pt (3-F) exhibited high antiproliferative effects (IC50 <2 μM). Drug lipophilicity and cellular accumulation were analyzed in an attempt to explain the differences in antitumor potency. To gain insight into their mode of action, DNA interaction studies were performed, in which compounds such as 1-Pt acted as non-DNA-binding platinum anticancer drugs, as neither intercalation nor DNA covalent binding were detected.
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin (Germany).
Maria T
MT
Proetto
Wukun
W
Liu
Andrey
A
Molchanov
William S
WS
Sheldrick
Adelheid
A
Hagenbach
Ulrich
U
Abram
Ronald
R
Gust
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010984:Platinum / Q000737:chemistry*; D012459:Salicylates / Q000737:chemistry*; D014783:Viscosity
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012459:Salicylates; C090416:salophen; D010984:Platinum; D004247:DNA
DNA interactions; cytotoxicity; drug accumulation; platinum complexes; salophene; schiff bases