Activity of platinum(II) intercalating agents against murine leukemia L1210

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.