title: Synthesis, biodistribution and antitumor activity of hematoporphyrin-platinum(II) conjugates.
abstract: A new series of platinum(II) complexes of pegylated hematoporphyrin derivatives with controlled hydrophobic/hydrophilic balance were synthesized by introducing different kinds of poly(ethylene glycol) and amine ligands to the porphyrin ring. The antitumor activity of the porphyrin-platinum(II) conjugates was assayed in vitro and in vivo against leukemia L1210 cell line and various human tumor cell lines. The present complexes exhibited high antitumor activity and improved water solubility as well as considerable lipophilicity. In particular, complex 16 showed not only higher in vivo activity (T/C%=258) than cisplatin (T/C%=184) and carboplatin (T/C%=168), but also excellent solubility in water and organic solvent. The antitumor activity of complex 20 was superior to that of carboplatin against all human tumor cell lines tested. Moreover, some amphiphilic complexes (7 and 12) exhibited elevated tumor-localizing effect (tumor/muscle ratio>2).
authors.affiliation: Department of Chemistry, Ewha Womans University, Seoul 120-750, South Korea.
authors.forename: Yeong-Sang
authors.initials: YS
authors.lastname: Kim
authors.forename: Rita
authors.initials: R
authors.lastname: Song
authors.forename: Dong
authors.initials: D
authors.lastname: Hyun Kim
authors.forename: Moo-Jin
authors.initials: MJ
authors.lastname: Jun
authors.forename: Youn-Soo
authors.initials: YS
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D006415:Hematoporphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D006415:Hematoporphyrins; D009944:Organoplatinum Compounds; D016190:Carboplatin