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.
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Authors | W D McFadyen, L P Wakelin, I A Roos, V A Leopold |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 28
Issue 8
Pg. 1113-6
(Aug 1985)
ISSN: 0022-2623 [Print] United States |
PMID | 4020833
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- DNA, Neoplasm
- Intercalating Agents
- Organoplatinum Compounds
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Topics |
- Animals
- Antineoplastic Agents
(chemical synthesis)
- Cell Division
(drug effects)
- Cells, Cultured
- DNA, Neoplasm
(metabolism)
- Intercalating Agents
(chemical synthesis)
- Leukemia L1210
(drug therapy, metabolism)
- Male
- Mice
- Organoplatinum Compounds
(chemical synthesis, pharmacology)
- Structure-Activity Relationship
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