Screening of ferulic acid related compounds as inhibitors of xanthine oxidase and cyclooxygenase-2 with anti-inflammatory activity

Abstract

The ferulic and gallic acid related compounds from natural origin were studied against xanthine oxidase and cyclooxygenase-2 along with their anti-inflammatory activity. The compounds gallic acid, ferulic acid, caffeic acid and p-coumaric acid revealed promising anti-inflammatory activity (30–40% TNF-α and 60–75% IL-6 inhibitory activity at 10 μM). Bioavailability of compounds were checked by in vitro cytotoxicity using CCK-8 cell lines and confirmed to be nontoxic, but found toxic at higher concentration (50 μM). Gallic, ferulic, caffeic acid was demonstrated potential dual inhibition toward xanthine oxidase and cyclooxygenase-2 as calculated by IC50: 68, 70.2, and 65 (μ/ml (xanthine oxidase) and 68.5, 65.2, and 62.5 μg/ml (cyclooxygenase-2), respectively. The structure activity relationship and in silico drug relevant properties (HBD, HBA, PSA, c LogP, ionization potential, molecular weight, EHOMO and ELUMO) further confirmed that the compounds were potential candidates for future drug discovery study, which was expected for further rational drug design against xanthine oxidase and cyclooxygenase.

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Acknowledgement

This study was supported by KU-Research professor program-2015, Konkuk University, Seoul, South Korea.

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Authors

Contributions

SHN performed the laboratory work including in vitro xanthine oxidase and cyclooxygenase-2 activity, also in silico study and data analysis. VB assisted in anti-inflammatory assays. DHK provided idea and project plan with subsequent editing and checking of manuscript data and SHN contributed to critical reading and writing of the manuscript.

Corresponding author

Correspondence to Young-Soo Keum.

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The authors declare no conflicts of interest.

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Nile, S.H., Ko, E.Y., Kim, D.H. et al. Screening of ferulic acid related compounds as inhibitors of xanthine oxidase and cyclooxygenase-2 with anti-inflammatory activity. Rev. Bras. Farmacogn. 26, 50–55 (2016). https://doi.org/10.1016/j.bjp.2015.08.013

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Keywords

  • Ferulic acid
  • Gallic acid
  • Xanthine oxidase
  • Cyclooxygenase
  • SAR
  • Gout