Synthesis and characterization of novel palladium(II) complexes of bis(thiosemicarbazone). Structure, cytotoxic activity and DNA binding of Pd(II)-benzyl bis(thiosemicarbazonate).
The preparation of palladium(II) complexes of 3,5-diacyl-1,2,4-triazole bis(thiosemicarbazone) (H2L2), 2,6-diacylpyridine bis(thiosemicarbazone) (H2L3) and benzyl bis(thiosemicarbazone) (H2L4) is described. The new complexes [PdCl2(H2L2)] (1), [PdCl2(H2L3)] (2) and [PdL4].DMF (3) have been characterized by elemental analyses and spectroscopic studies (IR, 1H NMR and UV-Vis). The crystal and molecular structure of PdL4.DMF (L = bideprotonated form of benzyl bis(thiosemicarbazone)) has been determined by single-crystal X-ray diffraction: green triclinic crystal, a = 10.258(5), b = 10.595(5), c = 11.189(5) A, alpha = 97.820(5), beta = 108.140(5), gamma = 105.283(5) degrees, space group P1, Z = 1. The palladium atom is tetracoordinated by four donor atoms (SNNS) from L4 to form a planar tricyclic ligating system. The testing of the cytotoxic activity of compound 3 against several human, monkey and murine cell lines sensitive (HeLa, Vero and Pam 212) and resistant to cis-DDP (Pam-ras) suggests that compound 3 might be endowed with important antitumor properties since it shows IC50 values in a microM range similar to those of cis-DDP [cis-diamminedichloroplatinum(II)]. Moreover, compound 3 displays notable cytotoxic activity in Pam-ras cells resistant to cis-DDP (IC50 values of 78 microM versus 156 microM, respectively). On the other hand, the analysis of the interaction of this novel Pd-thiosemicarbazone compound with DNA secondary structure by means of circular dichroism spectroscopy indicates that it induces on the double helix conformational changes different from those induced by cis-DDP.
Matesanz
A I
AI
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Pérez
J M
JM
Navarro
P
P
Moreno
J M
JM
Colacio
E
E
Souza
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D002945:Cisplatin / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004351:Drug Resistance; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D014709:Vero Cells
D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; C403276:benzyl bis(thiosemicarbazone)palladium(II); D010165:Palladium; D004247:DNA; D002945:Cisplatin