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Synthesis, structural elucidation, and in vitro antiproliferative activities of mixed-ligand titanium complexes

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Abstract

Mixed-ligand titanium complexes have been synthesized by reacting titanium tetrachloride (TiCl4), benzoylacetone (bzac), and respective bidentate ligands [2,2′-bipyridine (bipy), 4,4′-dimethyl-2,2′-bipyridine (bpme), 4,4′-dimethoxy-2,2′-bipyridine (bpome), 6,6′-dimethyl-2,2′-bipyridine (dpme)], in 1:1:1 molar ratios, respectively. The structure of synthesized complexes was confirmed by different spectroscopic techniques like FT-IR, UV–Visible, NMR (1H and 13C), and mass spectrometry. The complexes were analyzed for antiproliferative potential in HeLa (cervical), C6 (glioma), and Chinese hamster ovarian (CHO) cell lines, and their effect was seen on different stages of the cell cycle only in CHO cells by using fluorescent propidium iodide. It was observed that all the four synthesized complexes exhibited potent cytotoxic activity toward Hela cancer cell line. The antiproliferative activity of complex TiCl2(bzac)(bpme) was found to be stronger against Hela with an IC50 value of 3.3 μM and weaker against C6 cell line having IC50 value of 141.7 μM. The flow cytometric analysis indicated that the complexes inhibited cell proliferation and increased in hypo diploid cells, which confirms to some extent the cell death via apoptosis.

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Acknowledgments

Authors thank Sophisticated Analytical Instrument Facility, Punjab University, Chandigarh, for recording NMR (1H and 13C) and mass spectra and center for material science and engineering, the National Institute of Technology, Hamirpur, Himachal Pradesh, India for recording FT-IR and UV–Vis spectra. We are also thankful to Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India for carrying out in vitro cytotoxic studies. One of the author Mr. Nitesh Kumar acknowledge MHRD, Government of India for Ph.D. fellowship. Financial assistance from CSIR and UPE (UGC) is also duly acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, National Institute of Technology, Hamirpur, 177005, Himachal Pradesh, India

    Nitesh Kumar, Raj Kaushal & Pamita Awasthi

  2. Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, Punjab, India

    Ashun Chaudhary & Saroj Arora

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  1. Nitesh Kumar
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  2. Raj Kaushal
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  3. Ashun Chaudhary
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  4. Saroj Arora
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  5. Pamita Awasthi
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Correspondence to Nitesh Kumar.

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Kumar, N., Kaushal, R., Chaudhary, A. et al. Synthesis, structural elucidation, and in vitro antiproliferative activities of mixed-ligand titanium complexes. Med Chem Res 23, 3897–3906 (2014). https://doi.org/10.1007/s00044-014-0963-7

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