Non-traditional platinum compounds for improved accumulation, oral bioavailability, and tumor targeting.
The five platinum anticancer compounds currently in clinical use conform to structure-activity relationships formulated (M. J. Cleare and J. D. Hoeschele, Bioinorg. Chem., 1973, 2, 187-210) shortly after the discovery that cis-diamminedichloroplatinum(II), cisplatin, has antitumor activity in mice. These compounds are neutral platinum(II) species with two am(m)ine ligands or one bidentate chelating diamine and two additional ligands that can be replaced by water through aquation reactions. The resulting cations ultimately form bifunctional adducts on DNA. Information about the chemistry of these platinum compounds and correlations of their structures with anticancer activity have provided guidance for the design of novel anticancer drug candidates based on the proposed mechanisms of action. This article discusses advances in the synthesis and evaluation of such non-traditional platinum compounds, including cationic and tumor-targeting constructs.
Lovejoy
Katherine S
KS
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Lippard
Stephen J
SJ
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002945:Cisplatin / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D018736:DNA Adducts / Q000737:chemistry; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D027702:Organic Cation Transporter 1 / Q000378:metabolism; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018736:DNA Adducts; D024243:HMGB1 Protein; D008024:Ligands; D027702:Organic Cation Transporter 1; D017671:Platinum Compounds; D002945:Cisplatin