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

• DOI: 10.1007/s00044-014-0989-x
• Publication Date: 2014-03-27T08:50:27Z
• Authors: Saqlain Haider; Mohammad Sarwar Alam; Hinna Hamid; Abhijeet Dhulap; Sadiq Umar; Mohammad Shahar Yar; Sameena Bano; Syed Nazreen; Yakub Ali; Chetna Kharbanda
• Keywords: Docking (animal); Proinflammatory cytokine

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.