1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 z Inorganic Chemistry DNA/Protein Binding, Molecular Docking and Cytotoxicity Studies of Piperazinyl-Moiety-Based Copper(II) Complexes Soumen Mistri, [a] Apu Patra, [a] Manas Kumar Santra, [b] Debasish Paul, [b] Ennio Zangrando, [c] Horst Puschmann, [d] and Subal Chandra Manna* [a] Copper(II) complexes {[Cu(HL)(ClO 4 )(H 2 O)](ClO 4 )⋅3H 2 O} (1), {[Cu (HL)(m-phth)]⋅5H 2 O} (2) and {[Cu(HL)(NCS)] 2 (ClO 4 ) 2 ⋅2H 2 O} (3) (HL = 2-{[2-(1-piperazinyl)ethylimino]methyl}phenol; m-phth = 1,3-benzenedicarboxylate] have been synthesized and charac- terized by structural determination and spectroscopic studies. The mononuclear square pyramidal complex 1 resulted from the reaction of HL with copper perchlorate hexahydrate. Then mononuclear square planar complex 2 and dinuclear thiocya- nato bridged complex 3 were obtained by reacting 1 with disodium 1,3-benzenedicarboxylate (Na 2 (m-phth)) and potassi- um thiocyanate, respectively. The interactions of 1–3 with CT- DNA / serum albumins were investigated by UV-visible absorption and fluorescence spectroscopy. The intrinsic bind- ing constants of 1, 2 and 3 with CT-DNA were calculated as 1.44 (� 0.13) × 10 5 , 4.86 (� 0.11) × 10 5 and 4.51 (� 0.16) × 10 5 L mol 1 , respectively. Study of the interactions of 1–3 with human serum albumin (HSA) / bovine serum albumin (BSA) showed that all the complexes could quench intrinsic fluorescence of HSA and BSA through a static quenching process. Molecular docking technique was utilised to confirm the mode of interaction of complexes with CT-DNA / serum albumin. Anticancer activities of the complexes have been tested using human breast cancer cell lines MCF7 and MBA- MB-231. Among the complexes studied 3 shows the higher cytotoxic activity and growth inhibition of cancer cells via induction of apoptotic cell death. Introduction Transition metal based Schiff base pharmaceuticals are promis- ing alternative for their potential application as DNA molecule probes and as chemotherapeutic agents for their possible application against cancer. [1–4] Cisplatin is one of the most important transition metal based pharmaceuticals being active as anticancer chemotherapeutic agent through induction of DNA and DNA protein binding. However, cisplatin has severe limitation due to several side effects such as hepato-, neuro- and nephrotoxicity. [4–6] To overcome these limitations many attempts have been taken to develop suitable alternative ways based on other metal ions, with improved pharmacological properties and aimed at different targets. In this regard, Schiff base compounds have gained considerable importance for their potential ability, significant biological and antitumor activity. [7–10] It is interesting to note that occasionally free Schiff compounds show less or no pharmaceutical activity in comparison to their metal complexes. [11–12] Owing to chelating nature of Schiff base ligands, they can effectively remove unintended effects of metal ions and can potentially deactivate either the carcinogenic metal or the enzyme, which is required for rapid growth of both malignant and cancer cells. Moreover, copper complexes exhibit a greater potential since the metal in different oxidation states can display various geometries and coordination numbers, better solubility and higher affinity for nucleobases. [13–16] Literature survey reveals that copper Schiff base complexes show significant level of anticancer, antibacterial, antiprolifer- ative and antimitotic activities for solid tumor metastases, sometimes displaying lower host toxicity in comparison to the well-known platinum compounds. [17–20] In addition studies of kinetics of interaction of DNA / serum albumin with copper coordination compounds are important to determine the affinities of copper compounds towards these biomolecules, providing information to support the development of efficient copper based pharmaceuticals. Over the last few years we have been working on the design and synthesis of copper(II) complexes. Here a piper- azinyl moiety based tridentate Schiff base (O,N,N donor set), 2- {[2-(1-piperazinyl)ethylimino]methyl}phenol (HL), was chosen for the synthesis of {[Cu(HL)(ClO 4 )(H 2 O)](ClO 4 )⋅3H 2 O} (1), {[Cu (HL)(m-phth)]⋅5H 2 O} (2) and {[Cu(HL)(NCS)] 2 (ClO 4 ) 2 ⋅2H 2 O} (3). The anticancer activity of these complexes towards MCF7 and MBA-MB-231 human breast cancer cells has been investigated. [a] Dr. S. Mistri, A. Patra, Dr. S. C. Manna Department of Chemistry and Chemical Technology, Vidyasagar Uni- versity, Midnapore 721102, West Bengal, India Fax: (91) (03222) 275329 Web: http://vidyasagar.ac.in/Faculty/Profile?fac_u_id = Fac-CHEM-8 E-mail: scmanna@mail.vidyasagar.ac.in [b] Dr. M. K. Santra, D. Paul National Centre for Cell Science, NCCS Complex, Pune University Campus Ganeshkhind, Pune-411 007, Maharashtra, India [c] Prof. E. Zangrando Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy [d] Dr. H. Puschmann Department of Chemistry, University of Durham, South Road, Durham DH1 3LE, U.K Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201801757 Full Papers DOI: 10.1002/slct.201801757 9102 ChemistrySelect 2018, 3, 9102 – 9112 © 2018 Wiley-VCH Verlag GmbH & Co. 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