. Nickel (II) complexes of naphthaquinone thiosemicarbazone and semicarbazone: Synthesis, structure, spectroscopy, and biological activity Zahra Afrasiabi a, * , Ekk Sinn a , Weisheng Lin a , Yinfa Ma a , Charles Campana b , Subhash Padhye c a Department of Chemistry, University of Missouri-Rolla, Rolla, MO 65409, USA b Bruker Analytical X-ray Division, Madison 53711, WI, USA c Department of Chemistry, University of Pune, Pune 411007, India Received 7 December 2004; received in revised form 11 April 2005; accepted 14 April 2005 Available online 31 May 2005 Abstract Ni(II) complexes of ortho-naphthaquinone thiosemicarbazone and semicarbazone were synthesized and spectroscopically char- acterized. The X-ray crystal structure of both the complexes describe a distorted octahedral coordination with two tridentate mono- deprotonated ligands. In vitro anticancer studies on MCF-7 human breast cancer cells reveal that the semicarbazone derivative along with its nickel complex is more active in the inhibition of cell proliferation than the thiosemicarbazone analogue. Ó 2005 Elsevier Inc. All rights reserved. Keywords: 1,2-Naphthaquinone; Thiosemicarbazone; Nickel complexes; Biological activity; MCF-7 breast cancer cells 1. Introduction Thiosemicarbazones (TSCs) have received consider- able attention because of their potential therapeutic activities against bacterial and viral infections [1,2], tuberculosis [3] and leprosy [4]. In addition particular attention has been given to their antitumor activity that seems to be due to inhibition of DNA synthesis caused by a modification in the reductive conversion of ribonu- cleotides to deoxyribonucleotides [5]. In a number of cases the transition metal complexes of TSCs showed greater biological activity than the uncomplexed ligands [6,7]. This observation further encouraged detailed studies on coordination chemistry involving TSCs [6,8,9]. In contrast to TSCs, less work has been reported on biological properties of their structural analogue, semic- arbazones (SCs). Recently it has been shown that SCs of aromatic and unsaturated carbonyl compounds have anticonvulsants properties and their great advantage over the analogues TSCs is their lesser neurotoxicity [10,11]. It is also reported that naftazone (1,2 naphtha- quinone semicarbazone) has an inhibitory effect on ni- tric oxide (NO) synthesis which protects the vascular system [12]. For the past few years we have been working on the structural and biological properties of metal complexes of the ortho-quinone thiosemicarbazones [13,14]. Re- cently we reported a mechanistical study on antitumor activity of naphthaquinone thiosemicarbazone (NQTS) metal complexes [15]. The results showed that the metal complexes could stabilize the cleavable complex formed by DNA and Topoisomerase II and the nickel (II) com- 0162-0134/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2005.04.012 * Corresponding author. Tel.: +1 573 341 4975; fax: +1 573 341 6033. E-mail address: za347@umr.edu (Z. Afrasiabi). www.elsevier.com/locate/jinorgbio Journal of Inorganic Biochemistry 99 (2005) 1526–1531 JOURNAL OF Inorganic Biochemistry