title: Activity of platinum(II) intercalating agents against murine leukemia L1210.
abstract: Four series of intercalating, square-planar Pt(II) complexes derived from the ligands 2,2'-bipyridine, 2,2':6',2"-terpyridine, 1,10-phenanthroline, and 3,4,7,8-tetramethyl-1,10-phenanthroline were synthesized and aspects of their activity against murine leukemia L1210 cells investigated. The 2,2':6',2"-terpyridine-thiolato complexes are growth inhibitory in culture, with IC50 values in the range 6-32 microM, and cause cell lysis at high concentrations. Of the remaining three series, the 2,2'-bipyridine complexes are the least potent in their effects. There is a general enhancement in activity on moving from the 1,10-phenanthroline complexes to the 3,4,7,8-tetramethyl-1,10-phenanthroline analogues. Flow cytometric analysis on representative complexes shows that they are not cell cycle specific. Alkaline elution experiments indicate no damage to DNA of cells exposed to (thiophenolato)(2,2':6',2"-terpyridine)platinum(II) chloride monohydrate and (ethylenediamine)(1,10-phenanthroline)platinum(II) dichloride dihydrate although (ethylenediamine)(3,4,7,8-tetramethyl-1,10-phenanthroline)platinum(II) dichloride dihydrate causes both single-strand breaks and DNA cross-links. Compounds 2a, 5a, and 6a showed no antitumor activity against L1210 in mice.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism; D007364:Intercalating Agents / Q000138:chemical synthesis*; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007364:Intercalating Agents; D009944:Organoplatinum Compounds