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In vitro and in vivo anti-proliferative evaluation of bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex against Ehrlich ascites carcinoma tumors

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Abstract

The bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex [Cu(ttpy)2]Cl2 was synthesized and authenticated by single crystal analysis, which shows distorted octahedral geometry around copper(II) ion. The crystal packing is stabilized by C–H···π inter and intramolecular interactions. The complex was found to be lipophilic as determined by shake-flask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially available anticancer drug cisplatin. Hoechst 33258, AO/EB and PI (flow cytometry) staining methods suggest that the complex can induce apoptosis in EAC cells. Cell cycle analyses also support the induced apoptosis. Cellular uptake studies revealed that the complex can go into the cytoplasm and accumulate in the cell nuclei. The complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway by activating caspase 3 and caspase 7 and regulates the Bcl-2 family proteins. In vivo study of the complex was validated against the animal tumor growth (EAC) cell in Swiss albino mice.

Graphical abstract

The bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway and significantly reduced the body weight and solid tumor volume in Swiss albino mice.

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Authors and Affiliations

  1. Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai, 600 014, India

    Dharmasivam Mahendiran & Aziz Kalilur Rahiman

  2. Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tiruchengodu, 637 205, India

    Raju Senthil Kumar

  3. CAS in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600 025, India

    Vijayan Viswanathan & Devadasan Velmurugan

Authors
  1. Dharmasivam Mahendiran
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  2. Raju Senthil Kumar
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  3. Vijayan Viswanathan
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  4. Devadasan Velmurugan
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  5. Aziz Kalilur Rahiman
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Correspondence to Aziz Kalilur Rahiman.

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Mahendiran, D., Kumar, R.S., Viswanathan, V. et al. In vitro and in vivo anti-proliferative evaluation of bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex against Ehrlich ascites carcinoma tumors. J Biol Inorg Chem 22, 1109–1122 (2017). https://doi.org/10.1007/s00775-017-1488-6

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  • DOI: https://doi.org/10.1007/s00775-017-1488-6

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