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Steroidal imidazoles: Synthesis, characterization, molecular docking studies with DNA and in vitro cytotoxicity

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Abstract

Bio-active steroidal imidazoles 7–9 were synthesised by reacting steroidal thiosemicarbazones 4–6 with phenacyl bromide. After characterisation by spectral and analytical data, the interaction of compounds 7–9 with DNA were carried out by UV-vis, luminescence spectroscopy and gel electrophoresis. The compounds bind with DNA preferentially through electrostatic and hydrophobic interactions with K b; 3.14 × 104, 6.27 × 104 and 5.17 × 104 M−1, respectively indicating higher binding affinity of compound 8 towards DNA. Gel electrophoresis depicted the concentration dependent cleavage activity of compound 8 with supercoiled pBR322. The docking study revealed the minor groove binding of compounds with DNA and intercalation between the nucleotide base pairs is due to imidazole moiety. In Dimethyl thiazolyl diphenyl tetrazolium bromide assay, compounds 7 and 8 showed promising activity against different human cancer cells especially against A545, HepG2 and MCF7 cells. The uptake of compounds by HepG2, MCF7 and A549 cells was studied by confocal microscopy. The Genotoxic nature of compounds 7 and 8 was studied by the comet assay while as the relative expressions of apoptotic markers of A545 cells after interacting with steroidal imidazoles was studied by western blotting analysis.

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Acknowledgements

Authors thank the Department of Chemistry, A.M.U., Aligarh, for providing necessary research facilities and the UGC for financial support in the form of research fellowship. Author (AMD) specially thank Prof. Shamsuzzaman for constant support, guidance as well as encouragement during the research programme.

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Authors and Affiliations

  1. Department of Chemistry, Aligarh Muslim University, Aligarh, 202 002, India

    Ayaz Mahmood Dar & Shams Uzzaman

  2. Department of Chemistry, Govt Degree College Kulgam, J&K, 192231, India

    Ayaz Mahmood Dar & Mir Shabeer Ahmad

  3. Department of Environment, Agriculture and Forestry, University of Helsinki, Helsinki, Finland

    Yusuf Khan

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  1. Ayaz Mahmood Dar
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  2. Shams Uzzaman
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  3. Mir Shabeer Ahmad
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Correspondence to Ayaz Mahmood Dar.

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Dar, A.M., Uzzaman, S., Ahmad, M.S. et al. Steroidal imidazoles: Synthesis, characterization, molecular docking studies with DNA and in vitro cytotoxicity. Med Chem Res 26, 372–383 (2017). https://doi.org/10.1007/s00044-016-1755-z

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