Exploring the scope of [Pt2(4-FC6H4) 4(μ-SEt2)2] as a precursor for new organometallic platinum(II) and platinum(IV) antitumor agents

Article abstract of DOI:10.1021/om5000908

The new compound [Pt₂(4-FC₆H₄) ₄(μ-SEt₂)₂] (A) was prepared and fully characterized. The reactions of compound A with ligands ArCH=NCH ₂CH₂NMe₂ (Ar = 2-BrC₆H₄, 1a; 2,6-Cl₂C₆H₃, 1b; 4-ClC₆H ₄, 1c; 2-Cl,6-FC₆H₃, 1d) were studied under different conditions and produced platinum(II) compounds [Pt(4-FC ₆H₄)₂(ArCH=NCH₂CH ₂NMe₂)] (2b-2d), containing a bidentate [N,N′] ligand, as well as cyclometalated platinum(IV) or platinum(II) compounds such as [PtBr(4-FC₆H₄)₂(C₆H ₄CH=NCH₂CH₂NMe₂)] (4a) or [PtCl{(3-FC₆H₃)(2-XC₆H₃)CH=NCH ₂CH₂NMe₂}] (5b: X = Cl; 5d: X = F), containing a tridentate [C,N,N′] ligand and either a five (4a) or a seven (5b, 5d) membered metallacycle. These compounds exhibit a great antiproliferative activity against non-small lung cancer cells (A549), and the best result was obtained for compound 2c (IC₅₀ = 0.3 ± 0.1 μM). While compounds 5 alter the mobility of plasmid DNA in a similar way to cisplatin, compound 4 was less efficient in removing the supercoils from DNA. In spite of the very low IC₅₀ value obtained for compound 2c, this compound does not interact with DNA, and it is neither an intercalator nor a topoisomerase I inhibitor.