Med Chem Res (2016) 25:2127–2132 DOI 10.1007/s00044-016-1625-8 MEDICINAL CHEMISTR Y RESEARCH ORIGINAL RESEARCH Design, synthesis, structural characterization and in vitro cytotoxic activity of mononuclear Ru(II)complexes Sreekanth Thota 1,2 ● Srujana Vallala 3 ● Rajeshwar Yerra 3 ● Daniel Alencar Rodrigues 2 ● Eliezer J. Barreiro 2 Received: 16 October 2014 / Accepted: 27 June 2016 / Published online: 26 July 2016 © Springer Science+Business Media New York 2016 Abstract The synthesis and characterization of ruthenium complexes (Ru-1–Ru-6) of the type [Ru(R) 2 (K)] 2+ (where R = 1,10-phenanthroline/2,2′-bipyridyl and K = acetyl coumarin-inh, pyrazole-tch, acetyl coumarin-tsz, are described. These ligands form bidentate octahedral ruthe- nium complexes. The in vitro cytotoxic activities of the complexes measurement against the human cancer T- lymphocyte cell lines. In vitro evaluation of these title complexes revealed cytotoxicity from 0.34 to 1.4 μg/mL against CEM, 0.28 to 1.8 μg/mL against L1210, 0.44 to 2.5 μg/mL against Molt4/C 8 , 0.98 to 1.6 μg/mL against HL60, and 0.66 to 1.4 μg/mL against BEL7402. Ruthenium com- plexes Ru-5 & Ru-6 showed that quite significant antic- ancer activities over standard drugs. Keywords Acetyl coumarin ● Ruthenium complexes ● Cytotoxicity Introduction Research on drugs based on ruthenium complexes is a fast developing field in medicine, especially in development of chemotherapeutic agents with less side effects and immu- nity to acquisition of drug resistance. (Muggia, 2009) The synthesis of ruthenium complexes with thiosemicarbazone ligands has been receiving considerable attention due to the pharmacological properties of both complexes & ligands. (Beckford et al., 2009; Mazumder et al., 2005; Thota et al., 2012) Thiosemicarbazone ligands exhibit a wide variety of biological activities such as antiviral (Finkielsztein et al., 2008), antitumor (Patel and Divatia, 2013), antibacterial (Agarwal et al., 2006), and antifungal properties (Costa et al., 2005). The thiosemicarbazone ligands usually coor- dinate to ruthenium through Nitrogen & Sulfur donor atoms in their (N, S) bidentate form. (Thota et al., 2013; El-shazly et al., 2006) Recently, two Ru(III) compounds, namely, KP1019 (indazolium trans-[tetrachloro bis (1H- indazole) ruthenate(III)] (Hartinger et al., 2008) and NAMI- A (imidazolium trans-[tetrachloro(dimethylsulfoxide)(1H- imidazole)-ruthenate(III)] entered phase II clinical trials as antimetastatic compounds. A series of ruthenium complexes having the general formula [Ru(S) 2 (K)], where S = 2,2′-bipyridine/ 1,10- phenanthroline and K = hfc, itsz, Meo-btsz, 4-Cl-btsz etc., reported (Karki et al., 2007). Complex [Ru (Phen) 2 (p-MOPIP)] 2+ can effectively inhibit the proliferation of Hep G-2 cell line with low IC 50 value (7.2–1.3 μM) (Schatzschneider et al., 2008), [Ru(Phen) 2 (DBHIP)] 2+ can effectively induce apoptosis of BEL-7402 cell lines (Liu et al., 2010). In recent year, several ruthenium-based com- plexes have been investigated such as chiral ruthenium complex [(1s, 2s)-DEPN]–RuCl 2 (PPh 3 ) 2 (Liu et al., 2010), new chiral—bridged diamine/diphosphine Ru(II) * Sreekanth Thota sthota@cdts.fiocruz.br 1 National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz - Ministério da Saúde, Av. Brazil 4036–Prédio da Expansão, 8° Andar—Sala 814, Manguinhos, Rio de Janeiro 21040-361 RJ, Brazil 2 Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil 3 S. R. College of Pharmacy, Department of Pharmaceutical Chemistry & Toxicology, Ananthasagar, Warangal 506371 Telangana, India