Interactions of the anticancer antibiotic altromycin B with copper(II), palladium(II) and platinum(II) ions and in vitro activity of the formed complexes.
Interaction of the anticancer antibiotic altromycin B with Cu(II), Pd(II) and Pt(II) ions was studied using 1H-NMR, EPR, electronic absorption and circular dichroism spectroscopy. The results derived from NMR studies where that the Pt(II) and Pd(II) ions interact with the nitrogen atom of the dimethylamino group of the C(10)-disaccharide, while the C(2)-epoxide group does not participate and remains intact. Cu(II) ions interact in a different way with altromycin B as was concluded by EPR and circular dichroism spectra. Altromycin B coordinates to the Cu(II) ions via the oxygen atoms of the C(11) phenolic and the C(12) carbonyl group while the nitrogen atom does not participate in the complexation. The presence of these metal ions improves the stability of altromycin B in solution. These complexes were studied in vitro against K562 leukemia sensitive and doxorubicin-resistant cells and GLC4 lung tumor cells, sensitive and doxorubicin-resistant. The activity of the complexes compared to the free drug is improved against resistant cells and is affected moderately against sensitive cells. Finally, 20% of platinum added as altromycin B metal complex entered GLC4 cells.
Nikolis
Nikolaos
N
Inorganic Chemistry Laboratory, Department of Chemistry, University of Athens, 15771, Panepistimiopolis, Athens, Greece.
Methenitis
Constantinos
C
Pneumatikakis
George
G
Fiallo
Marina M L
MM
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium / Q000378:metabolism*; D010984:Platinum / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; C063717:altromycin B; D010984:Platinum; D010165:Palladium; D003300:Copper