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In vitro and in silico exploration of IL-2 inhibition by small drug-like molecules

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Abstract

Interleukin-2 (IL-2) is an immunoregulatory cytokine produced by T lymphocytes in response to antigen. It is a potent growth and differentiation factor for several cell-types and is structurally related to the four-helix bundle family of cytokines. Here, we report IL-2 inhibitory potential and computational studies on different series of chalcones, benzothiazepines, semicarbazones, and dihydropyrimidines. These compounds were synthesized in wet lab and were then tested for their potency as IL-2 inhibitors through in vitro T cell proliferation, IL-2 cytokine production as well as their effect on oxidative burst. Compounds that showed significant suppressive activity were further evaluated for their cytotoxicity on normal two cell lines. Most of the chalcones were found to have a powerful inhibitory effect on T-lymphocytes proliferation and cytokine production. Among the aza heterocycles benzothiazepines, benzoxazepines, and benzodiazepinones were found to be the strongest IL-2 inhibitors. Molecular docking and MD simulation studies were carried out to correlate experimental and theoretical results whereby a good correlation was observed which indicated that computational studies could provide an alternate tool for the identification and designing of more potent IL-2 inhibitors.

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Acknowledgments

The authors Farzana Latif Ansari, Zaheer-ul-Haq, and Saima Kalsoom acknowledge the Higher Education Commission, Islamabad, Pakistan for providing financial support to conduct this study.

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Authors and Affiliations

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

    Saima Kalsoom, Awais Shaukat & Farzana Latif Ansari

  2. Department of Chemistry, Hazara University, Mansehra, 21120, Pakistan

    Umer Rashid

  3. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Omer Mohamed Abdalla, Khalida Hussain, Waqasuddin Khan, Mohammad Ahmad Mesaik &  Zaheer-ul-Haq

  4. Nanoscience and Catalysis Division, National Center for Physics, Quaid-i-Azam University, Islamabad, 44000, Pakistan

    Samina Nazir

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  1. Saima Kalsoom
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Correspondence to Farzana Latif Ansari.

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Kalsoom, S., Rashid, U., Shaukat, A. et al. In vitro and in silico exploration of IL-2 inhibition by small drug-like molecules. Med Chem Res 22, 5739–5751 (2013). https://doi.org/10.1007/s00044-013-0564-x

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  • DOI: https://doi.org/10.1007/s00044-013-0564-x

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