Synthesis, DNA-/bovine serum albumin-binding affinity, and cytotoxicity of dinuclear platinum(II) complexes with 1,6-naphthyridine-bridging ligand

The dinuclear platinum(II) complexes, [{PtCl(NH3)(2)}(2)(mu-1,6-nphe)](ClO4)(2) (Pt1) and [{Pt(en)Cl}(2)(mu-1,6-nphe)](ClO4)(2) (Pt2) (en is a bidentate-coordinated ethylenediamine and 1,6-nphe is the bridging 1,6-naphthyridine ligand) were synthesized and characterized by different spectroscopic methods. The DNA-binding evaluation of complexes Pt1 and Pt2 was done by UV-Vis, fluorescence emission spectroscopy, and their interaction with bovine serum albumin (BSA). The cytotoxic activity of these complexes was determined against mouse breast (4T1) and colon (CT26) cancer cell lines, human breast (MDA-MB-468), colon (HCT-116), and lung (A549) cancer cell lines as well as mouse mesenchymal stem cells (mMSC). Complex Pt1 showed higher cytotoxic capacity toward solid cancer cell lines compared with Pt2 and lower cytotoxic capacity toward mMSC cells compared with cisplatin. Furthermore, molecular mechanism studies showed that Pt1 complex induced 4T1 and A549 cell apoptosis therefore increasing expression of pro-apoptotic caspase-3 and decreasing expression of anti-apoptotic Bcl-2 and Ki-67. Antitumor capacity of Pt1 complex might be manifested at least in two ways: by facilitating apoptosis and by inhibiting tumor cells proliferation.

Automated summary

The dinuclear platinum(II) complexes Pt1 and Pt2 were synthesized and characterized, with Pt1 showing higher cytotoxicity towards solid cancer cell lines and lower cytotoxicity towards mMSC cells compared to Pt2. Furthermore, Pt1 complex induced apoptosis in 4T1 and A549 cells by increasing pro-apoptotic caspase-3 expression and decreasing anti-apoptotic Bcl-2 and Ki-67 expression, suggesting its potential antitumor capacity through facilitating apoptosis and inhibiting tumor cell proliferation.