Synthesis, Structure, and Anticancer Activity of Symmetrical and Non-symmetrical Silver(I)-N-Heterocyclic Carbene Complexes

Abstract

Synthesis and anticancer studies of three symmetrically and non-symmetrically substituted silver(I)-N-Heterocyclic carbene complexes of type [(NHC)2-Ag]PF6 (7–9) and their respective (ligands) benzimidazolium salts (4–6) are described herein. Compound 5 and Ag-NHC-complex 7 were characterized by the single crystal X-ray diffraction technique. Structural studies for 7 showed that the silver(I) center has linear C-Ag-C coordination geometry (180.00(10)o). Other azolium and Ag-NHC analogues were confirmed by H1 and C13-NMR spectroscopy. The synthesized analogues were biologically characterized for in vitro anticancer activity against three cancer cell lines including human colorectal cancer (HCT 116), breast cancer (MCF-7), and erythromyeloblastoid leukemia (K-562) cell lines and in terms of in vivo acute oral toxicity (IAOT) in view of agility and body weight of female rats. In vitro anticancer activity showed the values of IC50 in range 0.31–17.9 μM in case of K-562 and HCT-116 cancer cell lines and 15.1–35.2 μM in case of MCF-7 while taking commercially known anticancer agents 5-fluorouracil, tamoxifen, and betulinic acid which have IC50 values 5.2, 5.5, and 17.0 μM, respectively. In vivo study revealed vigor and agility of all test animals which explores the biocompatibility and non-toxicity of the test analogues.

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Acknowledgments

The authors are thankful to Higher Education Commission (HEC) of Pakistan for providing grant National Research Programme for Universities No. NRPU-8396 & NRPU-8198. They are also very much obliged to Rosenani A. Haque, School of Chemical Sciences as well as to Mohamed B. Khadeer Ahamed and Amin M. S. Abdul Majid of EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences of Universiti Sains Malaysia, 11800 USM, Penang, Malaysia for their technical support and proof-reading of the manuscript.

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Correspondence to Muhammad Adnan Iqbal.

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Appendix A Supplementary Material

Appendix A Supplementary Material

CCDC 916242 and 916239 contain the supplementary crystallographic data. The supplementary crystallographic data for salt 5 and carbene complex 7 is available free of charge at CCDC 916242 and 916239 of Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ,UK; fax (+44) 1223–336-033 or e-mail deposit@ccdc.cam.ac.uk or using link http://www.ccdc.cam.ac.uk/conts/retrieving.html. Moreover, the effects of increasing amounts of test compound on the percentage inhibition of cell proliferation are also available.

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Atif, M., Bhatti, H.N., Haque, R.A. et al. Synthesis, Structure, and Anticancer Activity of Symmetrical and Non-symmetrical Silver(I)-N-Heterocyclic Carbene Complexes. Appl Biochem Biotechnol 191, 1171–1189 (2020). https://doi.org/10.1007/s12010-019-03186-9

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Keywords

  • In vivo acute oral toxicity (IAOT)
  • MCF-7
  • K-562
  • HCT 116
  • Ag-NHC
  • Single crystal X-ray diffraction