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Design, synthesis and docking studies of 2-benzoxazolinone-based 1,2,4-triazoles as proinflammatory cytokine inhibitors

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Abstract

A library of 20 novel benzoxazolinone-based 1,2,4-triazoles has been synthesised and screened for their in vivo anti-inflammatory and antinociceptive activities. The compound 18e exhibited potent anti-inflammatory activity with 68.75 and 55.20 % inhibition in comparison to indomethacin which showed 65.62 and 60.41 % inhibition after 3 and 5 h, respectively. The five active compounds, i.e. 2a and 17e–20e showing significant in vivo anti-inflammatory activity have been screened for their in vivo COX-2, TNF-α, IL-1β and NO inhibitory activities. The COX-2 selectivity index of 17e was found to be 42.30 and thereby showing a high selectivity towards COX-2 inhibition. In silico molecular docking studies have been done in order to get an insight into the binding modes of these molecules with TNF-α protein. The compound 20e exhibited potent antinociceptive activity with 56.70 % inhibition of analgesia. The compounds 2a and 17e–20e did not exhibit any gastric ulceration.

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Acknowledgments

The authors thank Dr. G. N. Qazi, Vice-Chancellor, Jamia Hamdard for providing necessary facilities to the Department of Chemistry. One of the authors (SH) is also thankful to CSIR for awarding the senior research fellowship.

Conflict of interest

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India

    Saqlain Haider, Mohammad Sarwar Alam, Hinna Hamid, Sameena Bano, Syed Nazreen, Yakub Ali & Chetna Kharbanda

  2. Unit for Research and Development of Information Products-CSIR, Pune, 411038, India

    Abhijeet Dhulap

  3. Department of Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India

    Sadiq Umar

  4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110 062, India

    Mohammad Shahar Yar

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  1. Saqlain Haider
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  2. Mohammad Sarwar Alam
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  3. Hinna Hamid
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  4. Abhijeet Dhulap
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Correspondence to Mohammad Sarwar Alam.

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Haider, S., Alam, M.S., Hamid, H. et al. Design, synthesis and docking studies of 2-benzoxazolinone-based 1,2,4-triazoles as proinflammatory cytokine inhibitors. Med Chem Res 23, 4250–4268 (2014). https://doi.org/10.1007/s00044-014-0989-x

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