title: Synthesis, characterization, and DNA modification induced by a novel Pt-berenil compound with cytotoxic activity.
abstract: In the present paper, we show that the reaction of the antipyranosomatid berenil drug with K2PtCl4 resulted in the synthesis of a covalent (Pt(II)-berenil compound of formula [Pt2Cl4(berenil)2]Cl4.4H2O as shown by IR, 1H, 13C, and 195Pt-NMR. The Pt-berenil compound was tested for in vitro antitumor activity against HL-60 and U-937 human leukemic cells. The results show that the LC70 values of the Pt-berenil are about two-fold lower than those of cis-DDP in both HL-60 and U-937 cell lines. Melting data of Pt-berenil:DNA and berenil:DNA complexes indicate that the platinated compound produces on a DNA secondary structure higher compaction than the berenil ligand. The mobility in agarose gels and the circular dichroism spectra of the compounds:DNA complexes revealed, moreover, that both induce drastic changes on a DNA secondary and tertiary structure. The total reflection X-ray fluorescence data showed, in additIon that DNA platination in Pt-berenil:DNA complexes occurs within minutes after addition of the drug, in contrast to what that observed in cis-DDP:DNA complexes. On the basis of these results, we propose that in Pt-berenil, the berenil ligand acts as a carrier of the active cis-P(II) centers towards DNA.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
authors.forename: V M
authors.initials: VM
authors.lastname: González
authors.forename: P
authors.initials: P
authors.lastname: Amo-Ochoa
authors.forename: J M
authors.initials: JM
authors.lastname: Pérez
authors.forename: M A
authors.initials: MA
authors.lastname: Fuertes
authors.forename: J R
authors.initials: JR
authors.lastname: Masaguer
authors.forename: C
authors.initials: C
authors.lastname: Navarro-Ranninger
authors.forename: C
authors.initials: C
authors.lastname: Alonso
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D018736:DNA Adducts / Q000737:chemistry; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects*; D004133:Diminazene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D004273:DNA, Neoplasm; D017671:Platinum Compounds; C003915:diminazene aceturate; D004133:Diminazene