title: Platinum (II) and (IV) spermidine complexes. Synthesis, characterization, and biological studies.
abstract: By reaction of K2PtCl4 with spermidine we have synthesized two tris-platinum covalent compounds of formula (PtI2)3(sper)2 and (PtCl2)3(sper)2, one ionic compound of formula (sperH3)2(PtCl4)3, and another one of a covalent nature of formula (PtCl2sperH)2 (PtCl4) having a partially protonated spermidine residue. Treatment of the tris-platinum compounds with hydrogen peroxide and hydrochloric acid led to the production of two compounds of formula cis-trans-cis-(PtIVCl2(OH)2)3(sper)2 and cis-(PtIVCl4)3(sper)2, respectively. All of them have been characterized by IR and 1H MNR spectroscopy and tested for their ability to interact with pUC8 plasmid DNA by the use of UV, CD, and electrophoretic techniques. The results suggest that all of these compounds modify the secondary structure of the double helix. We observed that the alteration in electrophoretic mobility of nicked and closed circular forms of DNA induced by the Pt(II) complexes is higher than that induced by the Pt(IV) complexes. The synthesized compounds were also assayed for antitumor activity in vitro against breast (MDA-MB468) and leukemia (HL-60) tumor cells. Only three of these complexes may be regarded as potential antitumor agents, since their ID50 values are lower than 10 micrograms/ml.
authors.affiliation: Departamento de Química, Universidad Autónoma de Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Navarro-Ranninger
authors.forename: P A
authors.initials: PA
authors.lastname: Ochoa
authors.forename: J M
authors.initials: JM
authors.lastname: Pérez
authors.forename: V M
authors.initials: VM
authors.lastname: González
authors.forename: J R
authors.initials: JR
authors.lastname: Masaguer
authors.forename: C
authors.initials: C
authors.lastname: Alonso
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013095:Spermidine / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D004247:DNA; D013095:Spermidine