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Synthesis, in vitro lipoxygenase inhibition, docking study and thermal stability analyses of novel indole derivatives

Non-isothermal kinetic study of potent LOX inhibitor N’-(diphenylmethylene)-2-(1H-indole-3-yl) acetohydrazide

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Abstract

A series of indole derivatives has been synthesized and biologically evaluated to identify potent new lipoxygenase (LOX) inhibitors. All selected indole derivatives were screened for their LOX inhibition studies. Most of compounds showed good in vitro LOX inhibition properties exhibiting IC50 values in the range of 53.61 ± 0.14 to 198.61 ± 0.11 μM (mean ± SEM), as compared to the standard inhibitor baicalein with IC50 value 22.4 ± 1.3 μM. Structure activity relationship has been discussed and docking stimulation of most active compound 4f has also performed. Thermal stability and melting point of indole derivatives have been performed by thermal gravimetric analysis and differential scanning calorimetry analysis under nitrogen atmosphere at heating rate of 20 °C min−1. Compound 4f bearing bis-phenyl moiety has been found to be the most potent (IC50 53.61 ± 0.14 μM) and thermally most stable among the tested compounds. Imine (C=N) was found to be the key moiety for increasing the thermal stabilities of indole derivatives. FT-IR, NMR and elemental analysis techniques were performed for structural characterization.

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Acknowledgments

We acknowledge Aamir Saghir for his guidance and Higher Education Commission and Ministry of Science and Technology Pakistan for financial support.

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Authors and Affiliations

  1. Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore, 54000, Pakistan

    Muhammad Yar, Lala Rukh Sidra & Nafeesa Mushtaq

  2. Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece

    Eleni Pontiki

  3. Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan

    Muhammad Ashraf & Rumana Nasar

  4. Department of Chemistry, Government College University, Lahore, 54000, Pakistan

    Islam Ullah Khan

  5. Department of Allied Sciences and Chemical Pathology, University of Health Sciences, Lahore, 54600, Pakistan

    Nasir Mahmood

  6. Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan

    Syed Ali Raza Naqvi & Zulfiqar Ali Khan

  7. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan

    Sohail Anjum Shahzad

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  1. Muhammad Yar
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Correspondence to Muhammad Yar.

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Yar, M., Sidra, L.R., Pontiki, E. et al. Synthesis, in vitro lipoxygenase inhibition, docking study and thermal stability analyses of novel indole derivatives. J IRAN CHEM SOC 11, 369–378 (2014). https://doi.org/10.1007/s13738-013-0308-3

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  • DOI: https://doi.org/10.1007/s13738-013-0308-3

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