The in vitro antitumor activity of oligonuclear polypyridyl rhodium and iridium complexes against cancer cells and human pathogens Basava Punna Rao A a , Uma A b , Chiranjeevi T b , M.S. Bethu c , Venkateswara Rao J c , Debojit Kumar Deb a , Biplab Sarkar a , Werner Kaminsky d , Mohan Rao Kollipara a, * a Centre for Advanced Studies in Chemistry, North-Eastern Hill University, Shillong, 793 022, India b Centre for Biotechnology, IST, Jawaharlal Nehru Technological University, Kukatpally, 500 085, India c Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India d Department of Chemistry, University of Washington, Seattle, WA, 98195, USA article info Article history: Received 29 August 2016 Received in revised form 28 September 2016 Accepted 11 October 2016 Available online 12 October 2016 Keywords: Dipyridylamine Rhodium Iridium Antibacterial and antiproliferative abstract Synthesis, characterization and biological activity of mono, bi and tri nuclear pentam- ethylcyclopentadienyl rhodium and iridium complexes with 1,3,5-tris(di-2-pyridylaminomethyl)benzene (L) ligand have been described. These complexes have general formula [(Cp*MCl) n L] nþ {M ¼ Rh; n ¼ 1 (1), n ¼ 2(2), n ¼ 3(3); M ¼ Ir; n ¼ 1(4), n ¼ 2(5), n ¼ 3(6)} and have been characterized by various spectroscopic techniques. Crystal structure of the complexes 1 , 2 and 4e6 has been obtained by single crystal X-ray diffraction analyses. The electronic transition and orbital occupation of complexes have been rationalized by density functional theory studies. The comparative abilities of bacterial inhibition and antiproliferative activity of complexes 1e6 towards four human pathogens (Staphylococcus aureus MTCC96; Escherichia coli MTCC739; Klebsiella pneumonia MTCC2653 and Pseudomonas aeruginosa MTCC2453) and four cancerous cells {B16F10 (Mouse melano carcinoma), THP-1 (human acute mono- cytic leukemia), PC3 (Human prostate carcinoma) and SK-OV-3 (Human ovarian carcinoma)} have been investigated by agar well diffusion method and MTT assay respectively. An in vitro cytotoxicity study of the complexes (2 and 3) found significant activity against B16F10 and THP-1 cancer cell lines. The structure-activity relationship on aforementioned cancer cell lines indicates that rhodium complexes are more active than iridium complexes. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Cisplatin is the one, which originated the metal-based anti- cancer activity for the coordination complexes since 1960 [1]. This led to development of platinum group [2] and non-platinum [3] group metal complexes as antitumor agents [4e6]. Some of these clinically approved drugs are causing the side effects, so that new drugs with less toxicity towards the normal cells are desirable. Rhodium and iridium are 9th group congeners attaining huge in- terest as chemotherapeutics with their biological properties. Half- sandwich rhodium and iridium complexes with various nitrogen donor ligands can catalyze the reactions inside cells [7e10]. Such a catalytic property of complexes has improved the drug resistance with a new mechanism of action, which is different from the cisplatin. For example, calmanga-fodipir [Ca 4 Mn(DPDP) 5 ] is in phase II clinical trials for treatment of metastatic colorectal cancer by the catalytic hydrogenation property [11]. Fish et al. studied that the catalytic hydride transfer from [Cp*Rh(bipy)H] þ to biomimetic NAD þ derivative to give the 1,4-NADH analogues, by using the external hydride source sodium formate [12e14]. The catalytic transfer of hydrogen reactions resulted in reduction of NAD þ mol- ecules inside the cell and this lead to the lower toxicity of metal complexes in smaller doses [7]. Half-sandwich metal complexes are good chemotherapeutic agents by enzyme inhibition due to their selective bio molecular recognition [15]. The selective inhibition and targeting active sites of protein kinases is also observed by the variation of metal which results the molecular diversity [16]. Meggers et al. reported that the half-sandwich organometallic ruthenium complex is selectively inhibiting the human repair enzyme MTH1 with a single digit nano-molar (6 nM) concentrations by the selective interaction (several hydrogen bond and van-der-Walls contacts) with the 8- * Corresponding author. E-mail address: mohanrao59@gmail.com (M.R. Kollipara). Contents lists available at ScienceDirect Journal of Organometallic Chemistry journal homepage: www.elsevier.com/locate/jorganchem http://dx.doi.org/10.1016/j.jorganchem.2016.10.018 0022-328X/© 2016 Elsevier B.V. All rights reserved. Journal of Organometallic Chemistry 824 (2016) 131e139