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Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni(II) complexes with N,N,N′-trisubstituted thioureas

JBIC Journal of Biological Inorganic Chemistry volume 20, pages 541–554 (2015)Cite this article

Abstract

A series of N,N,N′-trisubstituted thioureas (1–12) and their Ni(II) complexes (1a–12a) were synthesized and characterized by multinuclear (1H and 13C) NMR, FT-IR spectroscopy and LC–MS techniques in combination with elemental analysis. The crystal structures of both ligands and Ni(II) chelates of type Ni(L-O, S)2 were determined by single crystal X-ray diffraction analysis. All the complexes were adopted to have square planar geometry, where the N,N,N′-trisubstituted thioureas showed bidentate mode of coordination at nickel centre through oxygen and sulfur atoms. The synthesized complexes were screened for potential inhibitors of Jack bean urease. Compounds 1a and 3a were observed as most potent inhibitors of urease exhibiting IC50 values of 1.17 ± 0.12 and 1.19 ± 0.41 µM, respectively. Cytotoxicity assay on lung carcinoma (H-157) and kidney fibroblast (BHK-21) cell showed that compounds were significant anticancer agents. Additionally, the complexes were tested against Leishmania major and found to be potent antileishmanial agents.

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Scheme 1
Fig. 1
Fig. 2

Abbreviations

ETDA:

Ethylenediaminetetraacetic acid

MTT:

3-(4 5-Dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide

PBS:

Phosphate-buffered saline

SRB:

Sulforhodamine B

TCA:

Trichloroacetic acid

TLC:

Thin layer chromatography

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Acknowledgments

The M. Khawar Rauf is thankful to the Quaid-e-Azam University, Islamabad, Pakistan, for the grant of funds for Post-doctoral Fellowship.

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Authors and Affiliations

  1. Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan

    Muhammad Khawar Rauf, Samad Yaseen, Amin Badshah,  Imtiaz-ud-Din & Jamshed Iqbal

  2. Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan

    Sumera Zaib, Raffia Arshad & Jamshed Iqbal

  3. Department of Biochemistry, Hazara University, Garden Campus, Mansehra, Pakistan

    Sumera Zaib

  4. Department of Physics, University of Sargodha, Sargodha, Pakistan

    Muhammad Nawaz Tahir

Authors
  1. Muhammad Khawar Rauf
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  2. Samad Yaseen
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Correspondence to Amin Badshah or Jamshed Iqbal.

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Rauf, M.K., Yaseen, S., Badshah, A. et al. Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni(II) complexes with N,N,N′-trisubstituted thioureas. J Biol Inorg Chem 20, 541–554 (2015). https://doi.org/10.1007/s00775-015-1239-5

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  • DOI: https://doi.org/10.1007/s00775-015-1239-5

Keywords

  • N,N,N′-trisubstituted thioureas
  • Nickel(II) complexes
  • Urease inhibition
  • Anticancer
  • Antileishmanial