Syntheses and Cytotoxicity of Pt(II) Complexes with Acyclovir

Sabina Grabnera*, Maja Čemažarb, Nataša Bukoveca, Gregor Seršab

aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia
bDepartment of Experimental Oncology, Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia

Acyclovir is an antiviral drug which acts against the viruses, including Herpes simplex 1 and 2 and Varicella-zoster. The novel cis-[PtI2(3-Hmpy)2](3-Hmpy=3-hydroxymethylpyridine)(2) and the water-soluble cationic Pt(II) complexes with acyclovir (acv, (9-[(2-hydroxyetoxy)methyl]guanine)), cis-[Pt(acv-N7)2(NH3)2]Cl2·2H2O (1) and cis-[Pt(acv-N7)2(3-Hmpy)2](NO3)2 (3), have been prepared and characterized by multinuclear NMR spectroscopy. The results of cytotoxicity assay of 1, 3 and cis-[PtCl2(NH3)2] (cisplatin, cDDP) performed in malignant melanoma B16 cells in vitro provide evidence that complex 1 and 3 are less cytotoxic compared to cisplatin. In vivo experiments performed on the same malignant melanoma B16 cells, grown as subcutaneous tumours, demonstrated that antitumour effectiveness of 1 was comparable to that of cisplatin.

Key words: Pt(II) complexes; acyclovir; cytotoxicity; tumour cells; melanoma