Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: comparison of effects of geometry and polyfunctionality on biological activity.
The synthesis of two new isomeric trifunctional dinuclear platinum complexes of formula [¿PtCl(NH(3))(2)¿micro-NH(2)(CH(2))(6)NH(2)-¿PtCl(2)(N H(3))¿](+) (1, 2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor cell lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH(3))(2)Cl(2)]) is described and compared with the profile for their bifunctional analogues, [¿cis/trans-PtCl(NH(3))(2)¿(2)micro-NH(2)(CH(2))(6)NH(2)](2+ ). The trifunctional dinuclear platinum complexes showed a unique profile of cytotoxicity against human cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell lines. The resistance factor is dependent on the geometry of the Pt coordination spheres - suggesting that these may be associated with DNA-binding modes. Retention of activity against CDDP-resistant cell lines and a different spectrum of activity compared to CDDP and also within different classes of polynuclear platinum complexes suggest that not only are they mechanistically different from mononuclear platinum complexes but also each individual class of polynuclear platinum structure may have its own unique character.
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Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284-2006, USA.
Rauter
H
H
Soares Fontes
A P
AP
Bandarage
R
R
Kelland
L R
LR
Farrell
N
N
D000588:Amines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010984:Platinum; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000588:Amines; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009942:Organometallic Compounds; D010984:Platinum