Analysis of two cycloplatinated compounds derived from N-(4-methoxyphenyl)-alpha-benzoylbenzylidenamine. Comparison of the activity of these compounds with other isostructural cyclopalladated compounds.
In the present paper we report the synthesis, structural characterization, biochemical properties, and antiproliferative activity of two organo-cis-platinum cyclometalated compounds of formula [M(4-OMeC6H4N=C(COC6H5)C6H4)X]2, where M = Pt and X=Cl (4) or OAc (5). The IR and 1H and 13C NMR data of the chloro-bridged compound 4 showed that it has a planar structure. As indicated by IR and 1H and 13C NMR, the acetate-bridged compound 5 has an open-book shape structure. This structure was further confirmed by X-ray diffraction. The comparison of the biochemical properties and antiproliferative activity of these compounds relative to the isostructural palladium compounds [Pd(4-OMeC6H4N=C(COC6H5)C6H4)X]2 [X = AcO (1) and (2) or Cl (3)] indicated that the activity of compounds 4 and 5 is higher than that of the corresponding isostructural compounds 3 and 1-2, respectively, since their ID50 are 2-9-fold lower. It seems that there are not differences in the antiproliferative activity of all these compounds against leukemia HL-60 cells or mammary cancer MDA-MB 468 cells. Compounds 4 and 5 modify also the DNA structure of the oc and ccc forms of plasmid DNA. The acetate-bridged compound 5 showed the highest antiproliferative activity which is even higher than that of cis-DPP. Our data indicate that the Pt(II) compounds are more active than those having Pd(II) as the metal center.
Navarro-Ranninger
C
C
Departamento de Química, Facultad de Ciencias, Universidad Autónoma de Madrid, España.
López-Solera
I
I
Pérez
J M
JM
Rodríguez
J
J
García-Ruano
J L
JL
Raithby
P R
PR
Masaguer
J R
JR
Alonso
C
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004270:DNA, Circular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007938:Leukemia / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010165:Palladium / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010957:Plasmids; D013055:Spectrophotometry, Infrared; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004270:DNA, Circular; D009944:Organoplatinum Compounds; C084668:bis(N-(4-methoxyphenyl)-alpha-benzoylbenzylideneamine)di-mu-chlorodiplatinum(II); C084667:bis(mu-(acetato-O:O'))bis(N-(4-methoxyphenyl)-alpha-benzoylbenzylideneamine)diplatinum(II); D010165:Palladium