Palladium(II) salt and complexes of spermidine with a six-member chelate ring. Synthesis, characterization, and initial DNA-binding and antitumor studies.
By reaction of spermidine trihydrochloride with K2PdCl4 and PdCl2 at different pH's, we have synthesized the [sperH3]2[PdCl4]3 (I), [PdCl2(sperH)]2[PdCl4] (II), and [(PdCl2)3(sper)2] (III) compounds. The structure of these compounds was studied by IR and 1H NMR; complex II was analyzed by x-ray diffraction. In this complex the spermidine is attached to the PdCl2 group forming a six-member chelate ring with a protonated terminal amine group. The crystal of [PdCl2(sperH)]2[PdCl4] x 2H2O (II) is monoclinic, P2(1)/n, with a = 7.023(1) A, b = 12.662(1) A, c = 18.435(3) A, and beta = 99.95(1) degrees, Z = 4, R = 0.051, and Rw = 0.058 on the basis of 2690 independent reflections. We have compared the antitumor activity in vitro against the isolated human breast carcinoma MDA-MB 468 cell line of compounds I, II, and III with that of cis-diamminedichloroplatinum(II), cis-DDP. The results show that compounds III and III have values of ID50 similar (0.74 microgram/ml) or even lower (0.56 microgram/ml) than cis-DDP (0.80 microgram/ml). We also observed that compounds I, II, and III have the ability to induce conformational changes in covalently closed circular (ccc) form of the pUC8 plasmid DNA. Compounds II and III also induce conformational changes in the open circular (oc) form of this plasmid.
Navarro-Ranninger
C
C
Departamento de Química, Universidad Autónoma de Madrid, Spain.
Zamora
F
F
Pérez
J M
JM
López-Solera
I
I
Martínez-Carrera
S
S
Masaguer
J R
JR
Alonso
C
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects; D010165:Palladium / Q000737:chemistry*; D010957:Plasmids; D013055:Spectrophotometry, Infrared; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D010165:Palladium; D004247:DNA; D013095:Spermidine