Structural studies and cytotoxic activity of N(4)-phenyl-2-benzoylpyridine thiosemicarbazone Sn(IV) complexes Anayive Perez-Rebolledo a , José Danilo Ayala a , Geraldo M. de Lima a , Nicoletta Marchini b , Gabriella Bombieri b , Carlos L. Zani c , Elaine M. Souza-Fagundes c , Heloisa Beraldo a, * a Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil b Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Viale Abruzzi 42, 20131 Milano, Italy c Centro de Pesquisas René Rachou-FIOCRUZ, 30190-002 Belo Horizonte, MG, Brazil Received 21 October 2004; accepted 24 January 2005 Available online 24 February 2005 Abstract Structural studies and an investigation of the cytotoxic activity of Sn(IV) complexes with N(4)-phenyl-2-benzoylpyridine thiosemicarba- zone (H2Bz4Ph) were carried out. The crystal and molecular structures of [Sn(2Bz4Ph)Cl 3 ]·CH 3 CH 2 OH (1) and [Sn(2Bz4Ph)BuCl 2 ]·H 2 O (Bu = butyl group) (2) were determined. Both compounds present octahedral coordination geometry with the 2Bz4Ph anionic ligand behaving as tridentate on the metal ion. A comparative study of the structures of these compounds along with that of [Sn(2Bz4Ph)Bu 2 Cl] (3) determined before is presented. The cytotoxicity of H2Bz4Ph and its Sn(IV) complexes was investigated against the MCF-7, TK-10 and UACC-62 human tumor cell lines. Among the three complexes, 3 proved to be better as cytotoxic agent than the clinically used drug etoposide. H2Bz4Ph and all complexes were able to induce apoptosis in UACC-62 cells. © 2005 Elsevier SAS. All rights reserved. Keywords: Thiosemicarbazones; Tin(IV) complexes; Crystal structures; Cytotoxic activity 1. Introduction Thiosemicarbazones and their metal complexes present a wide range of bioactivities, and their chemistry and pharma- cological applications have been investigated [1,2]. Thiosemi- carbazones derived from 2-formyl and 2-acetylpyridine have been extensively studied by other authors [3–6] and by some of us [7–11]. A few complexes of 2-benzoylpyridine thiosemi- carbazones were studied [12–16]. The literature reports that some N(4′)-dialkyl 2-benzoylpyridine thiosemicarbazones and their copper(II) complexes are active against human pathogenic fungi [12]. In a previous work we prepared 2-benzoylpyridine-derived thiosemicarbazones and a series of their 3d metal complexes. The ligand presented in vitro antifungal activity against Candida albicans, but this activity decreases or is lost on coordination [17]. Tin complexes are known for their interesting multiple applications as antitumorals, antibacterials, antifungals and biocides [18–20]. Coordination of tin with thiosemicarba- zones could in principle give complexes with the therapeutic properties of both metal and ligands. Recently some of us reported the spectral characterization and an investigation of the antifungal activity of N(4)-phenyl- 2-benzoylpyridine thiosemicarbazone (H2Bz4Ph) and its tin(IV) complexes [Sn(2Bz4Ph)Cl 3 ]·CH 3 CH 2 OH ( 1), [Sn(2Bz4Ph)BuCl 2 ]·H 2 O(2) and [Sn(2Bz4Ph)Bu 2 Cl] (3) (2Bz4Ph is the anionic ligand, formed upon deprotonation at N(3) and Bu = butyl group) [21]. Among the three com- plexes, 1 proved to be the most active as antifungal against C. albicans. In the present work we report a structural study of com- plexes 1 and 2 as well as an investigation of the cytotoxicity of H2Bz4Ph and of complexes 1–3 against the MCF-7, TK-10 and UACC-62 human tumor cell lines. 2. Results and discussion 2.1. Crystal and molecular structures Table 1 lists crystal data and structure refinement for com- plexes 1 and 2. Tables 2 and 3 list selected bond lengths and * Corresponding author. E-mail address: hberaldo@ufmg.br (H. Beraldo). European Journal of Medicinal Chemistry 40 (2005) 467–472 www.elsevier.com/locate/ejmech 0223-5234/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.ejmech.2005.01.006