Structure-cytotoxicity relationship for different types of mononuclear platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine

To compare the in vitro cytotoxicity of platinum(II) complexes with 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), three complexes were prepared: cis-[PtI2(dbtp)2] (1), cis-[Pt(NO3)2(dbtp)2] (2) and cis-[Pt(C4H4O5)(dbtp)2] (3). The coordination compounds have been structurally characterized by IR; 1H, 13C, 15N, 195Pt NMR and single-crystal X-ray diffraction (1). Spectroscopic studies reveal the monodentate coordination of the heterocycle ligand (dbtp) via N(3) to platinum(II) ions. In addition, the crystal structure of (1) shows that the platinum(II) ion is located in nearly square-planar PtI2N2 environments with two heterocycle ligands (dbtp) arranged in a head-to-head orientation. The complexes have been screened for their cytotoxicity against two human cells: non-small cell lung carcinoma (A549) and breast cancer (T47D). All of the complexes demonstrated a significant antiproliferative activity against both cell lines. On the basis of these results, it is concluded that the cytotoxicity of the studied compounds against T47D follows the order: (3) < (1) < (2).

Three complexes: cis-[PtI2(dbtp)2] (1), cis-[Pt(NO3)2(dbtp)2] (2) and cis-[Pt(C4H4O5)(dbtp)2] (3), in which dbtp is 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), were prepared and characterized by IR; NMR (1H, 13C, 15N, 195Pt) and X-ray. The molecular structure indicates that Pt(II) ion has the square planar geometry with two N(3) bonded dbtp in cis position. However, the cytotoxicity of the studied compounds against T47D follows the order: (3) < (1) < (2).Figure optionsDownload as PowerPoint slideHighlights
► Platinum(II) coordination compound as bioinorganic chemiotherapeutic prodrugs.
► 15N NMR can be used to determinate a coordination mode of triazolopyrimidine.
► Significant cytotoxic activity in vitro against T47D and A549 than cisplatin.
► Influence of different leaving group on cytotoxicity.