Synthesis, characterization, cytotoxic, and DNA binding studies of some platinum (II) complexes of 1,2-diamine and alpha-diimine with 2-pyridinecarboxylate anion.
Seven new water-soluble cationic complexes of general formula [Pt(2-pyc)(N-N)]+ (where N-N is 2NH3, ethylenediamine (en), 1,2-diaminopropane (1,2-dap), 1,3-diaminopropane (1,3-dap), (+/-) trans-1,2-diaminocyclohaxane (dach), 2,2'-dipyridylamine (dpa) or 1,10-phenanthroline (phen), and 2-pyridinecarboxylate anion) have been prepared. These complexes have been characterized by conductance measurements, and by ultraviolet-visible, infrared (IR), and 1H nuclear magnetic resonance (NMR) spectroscopy. The COSY (correlated spectroscopy) spectra of [Pt(2-pyc)(dpa)]+ and [Pt(2-pys)(dpa)]+ further support the structures of the above complexes with three nitrogen and one oxygen donor atoms in the first coordination sphere of platinum(II) with 1,2-diamine or alpha-diimine and 2-pyridinecarboxylate anion behaving as bidentate ligands. One of the compounds, [Pt(2-pyc)(dpa)]Cl, also shows a birefringence property in water. These compounds inhibit the growth of P388 lymphocytic leukemia cells. [Pt(2-pyc)(dpa)]+ shows I.D.50 value comparable to cisplatin. However, six other complexes show higher I.D.50 values than cisplatin. In addition, the inhibition studies also suggest that their target is DNA. Therefore, the interactions of four of the above complexes with calf thymus DNA have been studied by ultraviolet and fluorescence spectral methods. These studies suggest that [Pt(2-pyc)(NH3)2]+ and [Pt(2-pyc)(1,2-dap)+ bind to DNA by noncovalent interactions. On the other hand, [Pt(2-pyc)(dpa)]+ and [Pt(2-pyc)(phen)]+ bind to DNA by covalent monofunctional binding. The latter two complexes have also been interacted with PUC19 DNA. The gel electrophoresis studies of these interactions suggest that these complexes bind to DNA, and this binding leads to a conformational change in DNA.
Paul
A K
AK
Department of Chemistry, Indian Institute of Technology, Bombay, India.
Srivastava
T S
TS
Chavan
S J
SJ
Chitnis
M P
MP
Desai
S
S
Rao
K K
KK
D000838:Anions; D000970:Antineoplastic Agents / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry; D015195:Drug Design; D007097:Imines / Q000737:chemistry; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D009942:Organometallic Compounds / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D010984:Platinum / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013053:Spectrophotometry / Q000379:methods; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000838:Anions; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D003959:Diamines; D007097:Imines; D009942:Organometallic Compounds; D011725:Pyridines; D010984:Platinum; D004247:DNA