Synthesis and antitumor activity of platinum complexes of protonated diamines |
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Authors: | Sheryl L Doran Abdul R Khokhar Miles P Hacker |
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Institution: | Department of Chemotherapy Research, M.D. Anderson Hospital and Tumor Institute, Houston, Tex. 77025, U.S.A.;Departments of Chemistry and Pharmacology, University of Vermont, Burlington, Vt. 05405, U.S.A. |
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Abstract: | Complexes of the formula cis-Pt(H~N)(L)Cl2], where (H~N) are the protonated diamines including 3-aminoquinuclidine, N-aminopiperidine, piperazine, N-methylpiperazine, 1,1,4-trimethylpiperazine, and N-methyl-1,4-diazabicyclo 2,2,2] octane (N-methyl-dabco) and L = SCN?, NO2?, Br?, and F?, were synthesized from the protonated diamine complexes, Pt(H~N)Cl3]. The antitumor activities of the complexes were evaluated in vitro against L1210 murine leukemia cells, and ID50 values for the L-substituted complexes were compared to values of the parent complexes. In each case it was found that replacement of a chloride ion by SCN?, NO2?, Br?, or F?, either reduced or completely eliminated antitumor activity. This effect is explained in terms of the trans-directing ability of the ligand, L, compared to chloride. The NO2-substituted complex of 3- aminoquinuclidine was tested in vivo and found to exhibit little or no antitumor activity. |
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Keywords: | Author to whom correspondence should be addressed |
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