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Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents

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Abstract

A series of furoxan-based nitric oxide releasing ibuprofen derivatives were synthesized and tested for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, and hepatotoxic properties. The compounds exhibited more protection than ibuprofen with regard to gastric toxicity. Among the tested compounds 4-[2-[2-(4-isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan and 4-[2-[2-(4-isobutylphenyl)propanoyl]hydrazinecarbonyl]-3-phenylfuroxan emerged as most active anti-inflammatory agents with reduced gastrotoxicity. The results showed that incorporation of NO donating group caused a moderate increase in anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent drug ibuprofen. A molecular docking study of all the compounds was also performed to provide the binding modes of COX-1 enzyme. Among all the titled compounds, 4-[2-[2-(4-isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan was found to be most potent and have high docking score showing favorable orientation within the COX-1 binding site.

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Acknowledgments

The authors are grateful to University Grants Commission (UGC) New Delhi for financial support F. No. 36-1-08/2008(SR). Authors are also thankful Central Instrumentation Facility (CIF) Faculty of Pharmacy for spectral analysis of compounds and to Dr. Ambrish Kumar Tiwari, In-charge animal house, Jamia Hamdard, for providing animals. The authors are also thankful to Dr. A. Mukharjee, MD, Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, for carrying out histopathological studies.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, 110 062, India

    Mohd Amir, Mohd Wasim Akhter & Ozair Alam

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  1. Mohd Amir
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  2. Mohd Wasim Akhter
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  3. Ozair Alam
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Correspondence to Mohd Amir.

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Amir, M., Akhter, M.W. & Alam, O. Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents. Monatsh Chem 147, 493–508 (2016). https://doi.org/10.1007/s00706-015-1557-x

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  • DOI: https://doi.org/10.1007/s00706-015-1557-x

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