Design and synthesis of butenolide-based amide derivatives as anti-inflammatory agents

• DOI: 10.1007/s00044-015-1404-y
• Publication Date: 2015-07-27T04:20:42Z
• Authors: Yakub Ali; Mohammad Sarwar Alam; Hinna Hamid; Asif Husain; Abhijeet Dhulap; Sameena Bano; Chetna Kharbanda; Syed Nazreen; Saqlain Haider
• Keywords: Butenolide; Anti-inflammatory; Amide; Ex vivo

Butenolide-based eighteen new amide derivatives (1–18) have been synthesized and evaluated for anti-inflammatory activity. The compounds 9, 17 and 4 exhibited significant in vivo inhibition of 84.69, 76.52 and 76.22 % inflammation, respectively, after 5 h without causing any damage to stomach and liver in comparison with the standard drug indomethacin which showed 79.04 % inhibition. The compounds showing potent anti-inflammatory activity were further evaluated for ex vivo TNF-α suppression. Compounds 9, 17 and 4 significantly suppressed TNF-α concentration to 74.83, 71.74 and 67.11 % as compared to indomethacin which exhibited a suppression of 69.01 %. Compounds 9 and 17 were also found to suppress the expression of COX-2 and NF-κB in the paw tissue. Moreover, compound 9 showed significant analgesic activity (57.03 %) which was comparable to indomethacin (61.03 %).