Syntheses and activity of some platinum(IV) complexes with N-methyl derivate of glycine and halogeno ligands against HeLa, K562 cell lines and human PBMC Tibor J. Sabo a , Vesna M. - Dinovic ´ a , Goran N. Kalud - erovic ´ a, * , Tatjana P. Stanojkovic ´ b , Goran A. Bogdanovic ´ c , Zorica D. Juranic ´ b a Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, P.O. Box 158, 11001 Belgrade, Serbia and Montenegro b Institute of Oncology and Radiology, 11000 Belgrade, Serbia and Montenegro c VINC ˇ A Institute of Nuclear Sciences, P.O. Box 522, Belgrade 11001, Serbia and Montenegro Received 11 July 2004; accepted 11 January 2005 Abstract Four platinum(IV) complexes, trans,trans-dichlorobis(N,N-dimethylglycinato)platinum(IV), trans,trans-[Pt(dmgly) 2 Cl 2 ](1) and trans,trans-dibromobis(N,N-dimethylglycinato)platinum(IV), trans,trans-[Pt(dmgly) 2 Br 2 ](2), as well as, trans,trans-dichlorobis(N- methylglycinato)platinum(IV), trans,trans-[Pt(sar) 2 Cl 2 ] (3) and trans,trans-dibromobis(N-methylglycinato)platinum(IV), trans,- trans-[Pt(sar) 2 Br 2 ](4) (with configuration index for all complexes OC-6–14), were synthesized and characterized by elemental analysis, infrared and 1 H NMR spectroscopy. In the aim to assess the selectivity in the antitumor action of these complexes, the antiproliferative action of these compounds was determined to human adenocarcinoma HeLa cells; to human myelogenous leukemia K562 cells and to normal immunocompetent cells; i.e., on human PBMC. The details of the crystal structure synthesized trans,trans-[Pt(sar) 2 Br 2 ] complex were also reported here. In the crystal structure of trans,trans-[Pt(sar) 2 Br 2 ], the Pt(IV) ion had a deformed octahedral coordination with both N-methylglycinates and bromides bonded trans to one another and with the N– Pt–Br bond angles of 84.1(4) and 95.9(4)°. The trans,trans-[Pt(sar) 2 Br 2 ] complex molecules form 2D-layers with multiple N–HÁÁÁO and C–HÁÁÁO hydrogen bonds. Ó 2005 Elsevier B.V. All rights reserved. Keywords: Platinum (IV) complexes; Bidentate ligands; Sarcosine; Crystal structure; Neoplastic cells; PBMC 1. Introduction The observation that neutral platinum coordination compounds inhibit division and cell growth has generated much interest in the potential value of inorganic drugs in the field of cancer chemotherapy [1–6]. Cisplatin has been shown to have potent antitumor activity and is nowadays routinely employed in the treatment of several cancers [7,8]. However, because of its severe side-effect a need for new platinum complexes has arisen, and several new derivatives have been synthesized and tested against var- ious tumor model systems, with the hope of discovering new drugs with improved properties [5]. In the most suc- cessful second-generation cisplatin analogs (i.e., carbo- platin), the chloride ligands have been replaced by a carboxylate. Therefore, there has been an increasing interest in platinum(IV) complexes with biologically important ligands, such as aminocarboxylate ligands [9], because of recent development of new Pt(IV)-containing anti-cancer drugs and the evidence that they may react with the DNA without being reduced to Pt(II) [1,2]. 0020-1693/$ - see front matter Ó 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2005.01.007 * Corresponding author. Tel.: +3811 3282 111/736; fax: +38111 638 785. E-mail address: goran@chem.bg.ac.yu (G.N. Kalud - erovic ´). www.elsevier.com/locate/ica Inorganica Chimica Acta 358 (2005) 2239–2245