Synthesis, spectral study and cytotoxicity of platinum(II) complexes with 2,9-disubstituted-6-benzylaminopurines.
A series of platinum(II) complexes with 2,9-disubstituted-6-benzylaminopurines has been prepared. The complexes have the following composition: cis-[Pt(Boh)(2)Cl(2)] (1), cis-[Pt(Oc)(2)Cl(2)] (2), cis-[Pt(Ros)(2)Cl(2)] (3), cis-[Pt(i-PrOc)(2)Cl(2)] (4), cis-[Pt(BohH(+))(2)Cl(2)]Cl(2) (5), cis-[Pt(OcH(+))(2)Cl(2)]Cl(2) (6), cis-[Pt(RosH(+))(2)Cl(2)]Cl(2) (7) and cis-[Pt(i-PrOcH(+))(2)Cl(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 ((1)H, (13)C, (15)N and (195)Pt) 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 microM.
Malon
Michal
M
Laboratory of Growth Regulators, Faculty of Science, Palacký University and Institute of Experimental Botany ASCR, Slechtitelů 11, CZ-783 71 Olomouc, Czech Republic.
Trávnícek
Zdenek
Z
Marek
Radek
R
Strnad
Miroslav
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D001593:Benzyl Compounds; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D007701:Kinetin / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D010984:Platinum / Q000737:chemistry* / Q000633:toxicity; D011687:Purines; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D011687:Purines; D010984:Platinum; C480551:benzylaminopurine; D007701:Kinetin