New Antioxidant Agents Bearing Carboxamide Moiety: Synthesis, Molecular Docking and in Vitro Studies of New Benzenesulfonamide Derivatives

Abstract

Oxidative stress occurs when oxygen radical formation and levels exceed those of antioxidants, potentiating cell responses such as apoptosis, tumorigenesis, and immune response. In an event of microbial invasion, there is a production of Reactive-Oxygen-Species (ROS), which when in excess can lead to oxidative stress. Some of these microorganisms are opportunistic pathogens implicated in chronic inflammatory conditions including cystic fibrosis. The synthesis, anti-inflammatory, antimicrobial and antioxidant activities of ten new derivatives of benzenesulfonamide bearing carboxamide functionality are herein reported. The base promoted reactions of the appropriate amino acids with substituted benzenesulfonyl chlorides gave the benzene sulphonamides (3a-j) in excellent yields. Palladium mediated amidation of the benzenesulfonamide (3a-j) and ethylamine gave the new carboxamides (4a-j) in excellent yield.All the compounds possessed good antioxidant activity but only compound 4e (IC50 0.3586 mg/mL) had comparable activity with vitamin C (IC50 0.2090 mg/mL). Compound 4e inhibited carrageenan-induced rat-paw edema at 95.58, 88.79, and 86.96 % each at 1 h, 2 h, and 3 h respectively. In the antimicrobial activity study, compound 4f (MIC 7.23 mg/mL) was most potent against E.coli, compound 4j (MIC7.11, 6.42 and 6.32 mg/mL) was the most active against S.aureus, P.aeruginosa and B.subtilis, compound 4h (MIC 7.12 and 6.48 mg/mL) was most active against S.typhi and C.albicans respectively, compound 4c (MIC 6.63 mg/mL) was the most active against A.niger.

Keywords

• benzenesulfonamide
• carboxamide
• antioxidant
• anti-inflammatory
• antimicrobial