Synthesis, spectral study and cytotoxicity of platinum(II) complexes with 2,9-disubstituted-6-benzylaminopurines

Abstract

A series of platinum(II) complexes with 2,9-disubstituted-6-benzylaminopurines has been prepared. The complexes have the following composition: cis-[Pt(Boh) 2Cl 2] ( 1), cis-[Pt(Oc) 2Cl 2] ( 2), cis-[Pt(Ros) 2Cl 2] ( 3), cis-[Pt( i-PrOc) 2Cl 2] ( 4), cis-[Pt(BohH +) 2Cl 2]Cl 2 ( 5), cis-[Pt(OcH +) 2Cl 2]Cl 2 ( 6), cis-[Pt(RosH +) 2Cl 2]Cl 2 ( 7) and cis-[Pt( i-PrOcH +) 2Cl 2]Cl 2 ( 8), where Boh = 2-(3-hydroxypropylamino)-6-benzylamino-9-isopropylpurine, Oc = 2-(2-hydroxyethylamino)-6-benzylamino-9-methylpurine, Ros = 2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine and i-PrOc = 2-(2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine. The complexes have been characterized by elemental analyses, conductivity measurements and their infrared, ES + mass (electrospray mass spectra in the positive ion mode) and NMR ( 1H, 13C, 15N and 195Pt) spectra. The results obtained from the physical studies, particularly from multinuclear NMR spectroscopy, show that in all the investigated complexes ( 1– 8), two molecules of purine derivative are coordinated to platinum via the N(7) atom of the imidazole ring in a cis-configuration. The prepared compounds have been screened for their in vitro cytotoxicity against G-361 (human malignant melanoma), HOS (human osteogenic sarcoma), K-562 (human chronic myelogenous leukemia) and MCF-7 (human breast adenocarcinoma) cell lines. All complexes are significantly more active than the initial 2,9-disubstituted-6-benzylaminopurine derivatives. In the case of some tumour cell lines, IC 50 values for the complexes ( 1, 3, 4, 5, 8) are significantly lower than those obtained for cisplatin and oxaliplatin. The best cytotoxicity was achieved for the complex ( 3) for which IC 50 values range from 1 to 2 μM.