Studies of interaction of trichloro{eta2-cis-N,N-dimethyl-1-[6-(N',N'-dimethyl-ammoniummethyl)-cyclohex-3-ene-1-yl]-methylammonium}platinum(II) chloride with DNA: Effects on secondary and tertiary structures of DNA. Cytotoxic assays on human ovarian cancer cell lines, resistant and non-resistant to cisplatin.
The studies of interaction with DNA and the cytotoxic activity of a new organometallic platinum(II) compound are presented. The ability of this new platinum complex to modify secondary DNA structure was explored by circular dichroism (CD). Electrophoretic mobility showed changes in tertiary DNA structure, and atomic force microscopy (AFM) revealed morphological changes of plasmid DNA (pBR322). This compound breaks the traditional structure-activity rules for cis-platinum compounds, but it could be of interest because of its different kinetics. An organometallic bond normally shows a trans-effect higher than that of an amine ligand, and that fact, a priori, could contribute to a higher DNA binding rate. Several ovarian cancer cell lines, resistant and non-resistant to cisplatin, were exposed to increasing concentrations of cisplatin and complex 5 for 24 h, after which time the cell number/viability was determined by the colorimetric MTT assay. A lower cytotoxicity but also a lower resistant factor was observed for organometallic compound 5 than for cisplatin, against A2780 and A2780cisR cell lines. This result is consistent with the DNA interaction degree observed by the aforementioned techniques.
Gay
Marina
M
Department of Organic Chemistry, Universidad de Barcelona, Campus de Pedralbes, Spain.
Montaña
Angel M
AM
Moreno
Virtudes
V
Prieto
María-José
MJ
Pérez
José Manuel
JM
Alonso
Carlos
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003124:Colorimetry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D018625:Microscopy, Atomic Force; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D004247:DNA; D002945:Cisplatin