Synthesis, characterization, and in vitro evaluation of a potentially selective anticancer, mixed-metal [ruthenium(III)-platinum(II)] trinuclear complex.
A new type of mixed-metal trinuclear complex containing platinum(II) and ruthenium(III) fragments that resemble both cisplatin and NAMI-A has been synthesized and characterized by IR, 1H NMR, elemental analysis, and X-ray crystallography. The water-soluble compound Na2{trans,cis,trans-[RuIIICl4(DMSO-S)(mu-pyz)]2PtIICl2} (AH-197, pyz = pyrazine) was assessed for its effects on DNA mobility and toxicity against human cancer cell lines. When compared to cisplatin and KP-1019 (which structurally resembles NAMI-A), IC50 results showed that AH-197 had an intermediate toxicity. When this data was coupled with a subsequent COMPARE evaluation (standard COMPARE queries resulted in insignificant correlation coefficients (<0.70) while very low COMPARE correlation coefficients were found in the matrix queries as well), AH-197 yielded a correlation coefficient of 0.19 when compared to cisplatin and 0.25 when compared to KP1019 indicating that AH-197 has a unique behavior.
Department of Chemistry, Bard College, Annandale-on-Hudson, NY 12504-5000, USA.
Amnon
A
Herman
Joseph M
JM
Tanski
Michael F
MF
Tibbetts
Craig M
CM
Anderson
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004247:DNA / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010957:Plasmids / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010984:Platinum; D012428:Ruthenium; D004247:DNA