Mononuclear half-sandwich cyclic-p-perimeter platinum group metal complexes having bithiazole ligands: Synthesis, molecular and anti- cancer studies Mahesh Kalidasan a , Scott Forbes b , Yurij Mozharivskyj b,⇑ , Maryam Ahmadi c , Zeynab Ahmadihosseini c , Roger M. Phillips c,⇑ , Mohan Rao Kollipara a,⇑ a Department of Chemistry, North Eastern Hill University, Shillong 793 022, India b Department of Chemistry and Chemical Biology, McMaster University, ON L8S 4M1, Canada c Department of Cancer Pharmacology, Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, United Kingdom article info Article history: Received 5 May 2014 Received in revised form 13 June 2014 Accepted 14 June 2014 Available online 3 July 2014 Keywords: Ruthenium Rhodium Iridium Arene ligands Bithiazole abstract Mononuclear cationic half-sandwich arene Ru(II) and Cp / Rh(III)/Cp / Ir(III) compounds with the general formula [(g 6 -arene)Ru(L)Cl] + and [Cp / M(L)Cl] + have been isolated by the reaction of bithiazole ligands {2,2 0 -dimethyl-4,4 0 -bithiazole (dm4bt), 2,2 0 -diamino-4,4 0 -bithiazole (da4bt), and 2,2 0 -diphenyl-4,4 0 - bithiazole (dp4bt)} with the precursor compounds [(g 6 -arene)Ru(l-Cl)Cl] 2 (arene = C 6 H 6 , p- i PrC 6 H 4 Me or C 6 Me 6 ) and [Cp / M(l-Cl)Cl] 2 (M = Rh, Ir). These compounds were isolated as SbF 6 salts and fully char- acterized by spectral studies. Some representative compounds were confirmed by single crystal X-ray crystallographic studies. Chemo-sensitivity activities of compounds 1, 5, 11, 12, 14 and 15 were evaluated against two human breast carcinoma cell lines (MDA-MB-231 and T47D). There is a clear SAR seen, where the iridium-based complexes with the dp4bt ligand are much more potent than the ruthenium and rhodium complexes. Ó 2014 Elsevier B.V. All rights reserved. 1. Introduction Cisplatin and its derivatives have achieved the treatment of cancer since 1965, where the chemotherapeutic success of such platinum compounds is undeniable. Cisplatin, though in clinical use, is not effective against many common types of cancers due to drug resistance and a deplorable range of side effects, which can include nerve damage, hair loss and nausea. This calls for the development of new metal-based anticancer agents with different mechanisms of action that can reduce side effects and overcome drug resistance to platinum-based chemotherapy. In the search for novel non-platinum metal-based anticancer therapeutic agents, the ruthenium-based drugs NAMI-A, KP1019 and RAPTA exhibit many appealing advantages and having successfully entered clini- cal trials. Such complexes appear to be the most promising alterna- tives to platinum-based drugs [1–5]. In recent years, the Sadler and Dyson research groups have investigated the anticancer properties of organometallic com- pounds [6], their work on organometallic Ru(II) arene complexes as potential anticancer agents [7–9] being noteworthy. More recently, organometallic Cp / Rh(III) and Cp / Ir(III) complexes have been shown to have good anticancer activity [10–13]. For example, Keppler and co-workers and Severin et al. have endeavored to develop metal based anticancer agents by introducing bioactive ligands containing various arenes, N,N- or N,O- or O,O-chelating ligands and mono-dentate leaving groups [14,15]. A number of research groups have focused on organometallic compounds con- taining various nitrogen-based bidentate ligands in their search for promising classes of anticancer agents [16]. Among the various nitrogen based N,N 0 -chelating ligands, bithiazole ligands have been interesting due to weak p-accepting property in comparison with bipyridine [17]. Moreover, the bithiazole moiety features as one domain in the structure of bleo- mycin (Fig. 1) that plays an important role in the interaction of ble- omycin with DNA. The bleomycins (BLMs) are a class of antitumor antibiotics, which are clinically used in the treatment of skin, head and testicular cancers [18]. Gras et al. have reported a study of activity of the [Cp / IrCl(pytz)]PF 6 complex towards A2750 cells in 2010, where pytz is 2-(pyridine-2yl)thiazole [9b]. To our knowl- edge there is still very limited study on the anticancer activity of bithiazole-containing Pt(II), Pd(II) and Au(III) complexes. Such compounds have been evaluated for cytotoxicity in nonmalignant http://dx.doi.org/10.1016/j.ica.2014.06.024 0020-1693/Ó 2014 Elsevier B.V. All rights reserved. ⇑ Corresponding authors. Tel.: +91 364 272 2620; fax: +91 364 2550076 (M.R. Kollipara). E-mail address: mohanrao59@gmail.com (M.R. Kollipara). Inorganica Chimica Acta 421 (2014) 349–358 Contents lists available at ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica