Synthesis, structures and antitumor activity of the first crown ester-linked bipyridyl platinum complexes.
Three new crown ester-linked bipyridine homologs with three, four or five ethylene glycol units, which are bulky and soluble in both hydrophilic and lipophilic media, were synthesized. The reaction of the appropriate macrocycles with K2PtCl4 in water gave yellow cisplatin analogs in good yield. These complexes were converted to carboplatin analogs by exchange of the leaving group. All the compounds were characterized by elemental analysis and various spectroscopic methods. Carboplatin analogs showed good solubility in both hydrophilic and lipophilic media. The crystal structure of 2c, the carboplatin analog with macrocycles containing five ethylene glycol units, was determined by X-ray diffraction: space group P1, a = 9.798(1), b = 12.580(3), c = 13.945(2) A, alpha = 108.61(2), beta = 94.59(1), gamma = 97.42(2) degrees, Z = 2, R = 0.0618. Some of platinum complexes showed a moderate cytotoxic effect on both murine leukemia L1210 and P388 even though they do not have any NH proton.
Yoo
J
J
Department of Chemistry, Korea Advanced Institute of Science and Technology, Taejon, South Korea.
Sohn
Y S
YS
Do
Y
Y
D015082:2,2'-Dipyridyl / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016190:Carboplatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D002945:Cisplatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D004988:Ethers, Cyclic; D009944:Organoplatinum Compounds; D015082:2,2'-Dipyridyl; D016190:Carboplatin; D002945:Cisplatin