Platinum(IV) complexes with purine analogs. Studies of molecular structure and antiproliferative activity in vitro

A series of tetrachloride platinum(IV) compounds of the general formulae PtCl4L2, where L = 1,2,4-triazolo[1,5-a]pyrimidine (tp) (1), 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine (dmtp) (2), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) (3) and 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) (4) have been prepared and characterized by thermal analysis, 1H, 13C, 15N, 195Pt NMR and IR spectroscopy. Spectral data suggest that the triazolopyrimidines act as a monodentate ligand via the nitrogen atom N(3). The preliminary assessments of antitumor properties of the four complexes were evaluated as in vitro antiproliferative activity against three cell lines: HL-60 human acute promyelocytic leukemia, SW707 rectal adenocarcinoma and HCV29T bladder cancer. PtCl4(dbtp)2 exhibits high cytotoxic activity against all human cell lines, whereas the other complexes are only moderately active.The crystal structure of [H2mtpO]2[PtCl6] (5) was determined using a single crystal X-ray diffraction method. The compound crystallized in the monoclinic group P21/n. The structure of (5) consists of (H2mtpO)22+ dimeric cations, protonated at the N(3) atom and linked by hydrogen bonding with octahedral [PtCl6]2− anions.

Graphical abstractHere, we described the platimum(IV) complexes containing 1,2,4-triazolo[1,5-a]pyrimidine as carrier ligands. Their structures are characterized by multinuclear NMR, IR spectroscopy and X-ray analysis. The platinum(IV) complexation results in a large shielding of 15N NMR signals of coordinated nitrogen atom (ca. 87–115 ppm) and proves that coordination of investigated 1,2,4-triazolo[1,5-a]pyrimidines occurs via N(3). In addition, PtCl4(dbtp)2 exhibits high cytotoxic activity and may be recommended for further preclinical studies.Figure optionsDownload full-size imageDownload as PowerPoint slide