Antiproliferative activity of Pt(II) and Pd(II) phosphine complexes with thymine and thymidine.
Oxidative addition reactions between [M(PPh(3))(4)] (M=Pt and Pd) and N1-methylthymine (t)/3',5'-di-O-acetylthymidine (T) were carried out to give [M(II)(PPh(3))(2)Cl t (or T)] complexes, in which the metal is coordinated to the N3 of the base. All complexes were characterized by spectroscopic analyses (IR, NMR) and Fast Atom Bombardment mass spectrometry (FAB-MS); X-ray data for the thymine complexes and elemental analysis for the thymidine complexes are reported. The antiproliferative activity of the complexes was tested on human chronic myelogenous leukaemia K562 cells. Arrested polymerase-chain reaction analysis was carried on to correlate antiproliferative activity and inhibition of DNA replication. All Pd and Pt complexes exhibit antiproliferative activity, Pd complexes resulting always more active than Pt complexes. Arrested PCR data are strongly in agreement with the effects on cell growth, suggesting that inhibition of the DNA replication by the synthesized compounds is the major basis for their in vitro antiproliferative activity.
Messere
Anna
A
Dipartimento di Scienze Ambientali, Seconda Università di Napoli, via Vivaldi 43, 81100 Caserta, Italy.
Fabbri
Enrica
E
Borgatti
Monica
M
Gambari
Roberto
R
Di Blasio
Benedetto
B
Pedone
Carlo
C
Romanelli
Alessandra
A
D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D010165:Palladium / Q000737:chemistry* / Q000494:pharmacology*; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology*; D013936:Thymidine / Q000737:chemistry; D013941:Thymine / Q000737:chemistry
D017931:DNA Primers; D010720:Phosphines; D010984:Platinum; D010165:Palladium; C044646:phosphine; D013941:Thymine; D013936:Thymidine