ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis, DFT calculations and characterisation of new mixed Pt(II) complexes with 3-thiolanespiro-5′-hydantoin and 4-thio-1H-tetrahydropyranspiro-5′-hydantoin

Adriana Bakalova, Boryana Nikolova-Mladenova, Rossen Buyukliev, Emiliya Cherneva, Georgi Momekov, and Darvin Ivanov

Department of Chemistry, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria

E-mail: adrigebk@abv.bg

Abstract: Cisplatin is an anticancer drug widely used in the treatment of a wide range of solid tumours (head and neck, lung, bladder etc.), testicular and ovarian cancers. Because of its severe toxicity profile and spontaneous development of drug resistance in tumours, a number of Pt(II) complexes have been synthesised and tested for anti-tumour activity. Some of the investigations have focused on using ligands bearing donor atoms other than N (e.g., S, P, O). Two new mixed Pt(II) complexes of the general formula cis-[Pt(NH3)LCl₂] where L is 3-thiolanespiro-5′-hydantoin and 4-thio-¹H-tetrahydropyranspiro-5′-hydantoin were synthesised. The complexes were studied by elemental analysis, melting points, IR and ¹H NMR spectra. The hybrid DFT calculations were used for optimisation of the structure geometries of the ligands III, IV and their Pt(II) complexes V and VI. The structural parameters so calculated, such as bond lengths and angles, are in good agreement with the experimental data for similar hydantoins and their platinum complexes. The results showed that the geometries of complexes V and VI are plane square and the bounding of ligands III and IV with platinum ions is effected by the sulphur atom from the cyclic ring. The complexes thus obtained were chemically examined in comparison with previously synthesised and published complexes of the general formula cis-[PtL₂Cl₂] (VII and VIII ) with the same ligands. The new compounds V and VI, as well as the previously investigated complexes (VII and VIII ), were analysed for cytotoxicity in vitro on SKW-3 and HL-60 human tumour cell lines. The results showed that all the complexes exerted concentration-dependent anti-proliferative activity.

Keywords: Pt(II) complexes – S-heterocyclic organic ligands – DFT calculations – cytotoxicity

Full paper is available at www.springerlink.com.

DOI: 10.1515/chempap-2015-0194

Chemical Papers 70 (1) 93–100 (2016)