ABSTRACT
[1,1-Cyclobutanedicarboxylato(2)-O,O'](1,3-dioxane-5,5-dimethan amine- N,N')platinum(II), 3a, a third generation, very water-soluble platinum complex, has been synthesized along with several of its analogues. All members of the new family contain a 1,3-dioxane or 1,3-dioxolane-1,3-diamine as their basic ligand, a moiety which contributes to their increased water solubility, and a bidentate acid ligand, which is responsible for their good stability. They were all easily crystallized and characterized by 1H NMR and elemental analysis, and the parent complex 3a was further characterized by 13C NMR. Their very desirable physical properties combined with their broad spectrum of antitumor activity and reduced toxicity make them good candidates of further development.
Subject(s)
Antineoplastic Agents/chemical synthesis , Dioxanes/chemical synthesis , Dioxins/chemical synthesis , Dioxolanes/chemical synthesis , Dioxoles/chemical synthesis , Organoplatinum Compounds/chemical synthesis , Animals , Antineoplastic Agents/therapeutic use , Carboplatin , Chemical Phenomena , Chemistry , Cisplatin/therapeutic use , Dioxanes/therapeutic use , Dioxolanes/therapeutic use , Female , Humans , Leukemia L1210/drug therapy , Leukemia P388/drug therapy , Mammary Neoplasms, Experimental/drug therapy , Melanoma, Experimental/drug therapy , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Organoplatinum Compounds/therapeutic use , Ovarian Neoplasms/drug therapy , Solubility , Structure-Activity RelationshipABSTRACT
The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-pyran-4,4- dimethanamine-N,N'-)platinum(II) have shown the greatest promise for further investigation and are currently under clinical evaluation.
Subject(s)
Antineoplastic Agents/chemical synthesis , Carboplatin/analogs & derivatives , Organoplatinum Compounds/chemical synthesis , Animals , Antineoplastic Agents/therapeutic use , Chemical Phenomena , Chemistry , Female , Humans , Mice , Mice, Nude , Models, Molecular , Neoplasm Transplantation , Neoplasms, Experimental/drug therapy , Organoplatinum Compounds/therapeutic use , Structure-Activity RelationshipABSTRACT
Bisamidines of 2,6-diaminoanthraquinone have demonstrated potent activity against cecal and hepatic Entamoeba histolytica infections in rats and hamsters, respectively. A number of these compounds compared favorably, in overall drug efficacy, with metronidazole and other standard agents.
