Synthesis and biological activity of novel platinum(II) complexes of glutamate tethered to hydrophilic hematoporphyrin derivatives.
A new series of hematoporphyrin-platinum(II) conjugates was prepared by platination of the glutamate ligand tethered to hydrophilic hematoporphyrin derivatives, in which different numbers of ethylene oxide unit were introduced to modulate the hydrophobic/hydrophilic balance of the conjugates. The antitumor activity of the hematoporphyrin-platinum(II) conjugates was assayed in vitro and in vivo against the leukemia L1210 cell line. Among the complexes, compound 11 exhibited not only higher in vivo activity (T/C% = 192) than cisplatin (T/C% = 184) and carboplatin (T/C% = 168), but also elevated tumor-localizing effect (tumor/muscle ratio > 3).
Kim
Yeong-Sang
YS
Division of Nano Science, Department of Chemistry, Ewha Womans University, Seoul 120-750, South Korea.
Song
Rita
R
Lee
Chong Ock
CO
Sohn
Youn Soo
YS
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018698:Glutamic Acid / Q000737:chemistry; D006415:Hematoporphyrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy; D051379:Mice; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D006415:Hematoporphyrins; D009944:Organoplatinum Compounds; D018698:Glutamic Acid