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Novel Derivatives of Rhodanine-3-Hippuric Acid as Active Inhibitors of Aldose Reductase: Synthesis, Biological Evaluation, and Molecular Docking Analysis

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Abstract

Inhibitors of aldose reductase provide a feasible mode of action against diabetic complications. Based on the marketed aldose reductase inhibitor epalrestat containing rhodanine nucleus, rhodanine-3-hippuric acid and its 5-arylidene derivatives were synthesized. The structure of newly synthesized compounds was confirmed by IR, 1H NMR, and 13C NMR spectrometry. In vitro aldose reductase inhibitory activity of the synthesized compounds was assayed and the results showed that most of the derivatives were potent against aldose reductase with IC50 values ranging from 0.2 to 2.36 µM. Two of the compounds with the highest efficacies among the tested compounds (IC50 values of 0.2 and 0.6 µM) were more potent than epalrestat. Molecular docking studies were undertaken to explore the binding modes of all compounds into the active site of aldose reductase in order to rationalize the inhibitory efficacy of these derivatives. Rhodanine-3-hippuric acid and all its arylidene derivatives fulfil Lipinski’s rule and show good drug-likeness property. In conclusion, novel compounds synthesized in the present study have proved to be potential drugs for diabetic complications.

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ACKNOWLEDGMENTS

We thank Karpagam Academy of Higher Education for providing instrumentation specialities to do the present research work. The authors are thankful to SAIF-STIC, Cochin University of Science and Technology, for their instrumentation support.

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Authors and Affiliations

  1. Department of Chemistry, Karpagam Academy of Higher Education, 641021, Coimbatore, India

    Stephen Kumar Celestina, Kaveri Sundaram & Subban Ravi

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  1. Stephen Kumar Celestina
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  2. Kaveri Sundaram
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  3. Subban Ravi
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Correspondence to Kaveri Sundaram.

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This article does not contain any studies involving human participants performed by any of the authors and does not contain any studies involving animals performed by any of the authors.

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The authors declare that they have no conflicts of interest.

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Corresponding author: e-mail: sundarg2010@gmail.com

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Stephen Kumar Celestina, Sundaram, K. & Ravi, S. Novel Derivatives of Rhodanine-3-Hippuric Acid as Active Inhibitors of Aldose Reductase: Synthesis, Biological Evaluation, and Molecular Docking Analysis. Russ J Bioorg Chem 45, 405–415 (2019). https://doi.org/10.1134/S1068162019050066

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