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Spectroscopic, Viscositic, DNA Binding and Cytotoxic Studies of Newly Synthesized Steroidal Imidazolidines

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Abstract

A series of new steroidal imidazolidine derivatives (4–6) were synthesized after reacting steroidal thiosemicarbazones with chloro ethylacetate in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (4–6) with DNA were carried out by UV–vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.63 × 103 M−1, 1.81 × 103 M−1 and 2.06 × 103 M−1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of imidazolidine moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds (4–6) revealed potential toxicity against the different human cancer cells (MTT assay). The uptake of compound 4 by MCF-7 and HeLa cells was studied by confocal microscopy which determined cell shrinkage and hence leading to the apoptosis. The results revealed that compound 4 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

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Acknowledgments

Authors thank Department of Chemistry and Biotechnology AMU Aligarh, for providing research facilities and biological results. Author (AMD) thank specially Prof. Shamsuzzaman for useful discussions and for successful completion of this work. Author (AMD) also thanks University Grants Commission India for successful completion of work.

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Authors and Affiliations

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

    Ayaz Mahmood Dar &  Shamsuzzaman

  2. Interdisciplinary Biotechnology Unit Aligarh Muslim University, Aligarh, 202002, India

    Shakir Khan

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  1. Ayaz Mahmood Dar
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  2. Shamsuzzaman
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  3. Shakir Khan
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Correspondence to Ayaz Mahmood Dar.

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Dar, A.M., Shamsuzzaman & Khan, S. Spectroscopic, Viscositic, DNA Binding and Cytotoxic Studies of Newly Synthesized Steroidal Imidazolidines. J Fluoresc 26, 639–649 (2016). https://doi.org/10.1007/s10895-015-1750-7

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  • DOI: https://doi.org/10.1007/s10895-015-1750-7

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