Carboxamides Bearing Sulfonamide Functionality as Potential Novel Phospholipase A <sub>2</sub> Inhibitors
Akachukwu Ibezim, Efeturi A. Onoabedje, Ifeyinwa C. Adaka, Kingsley O. Omeje, Ufuoma Shalom Onoabedje, C. Bonaventure
Abstract
Abstract Phospholipase A 2 (PLA 2 ) is a well‐known drug target for the treatment of inflammation‐related diseases. In this study, we reported the synthesis and biological screening of a series of new carboxamides bearing sulfonamide functionality for PLA 2 inhibitory potency and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging activity. Also, computational technique was employed to characterize the binding poses of top‐ranking derivatives. The biological assay shows that all the compounds inhibited the enzyme at percentage inhibition ranging from 5.3 to 66.4 %, while only six compounds inhibited more than 60.0 % of PLA 2 activity. The six derivatives also scavenge more than 60 % of the free radical which indicates they are both potential anti‐inflammatory and anti‐oxidant candidates. Analysis of the compounds’ theoretical binding poses reveals unique binding interactions exploitable in developing enhanced PLA 2 inhibitors.