SYNTHESIS, IN-VITRO ANTIOXIDANT, ANTIBACTERIAL ACTIVITIES OF NOVEL SULFONAMIDES FROM 5-AMINOSALICYLIC ACID: PROTECTIVE EFFECT OF SELECTED SULFONAMIDES ON ACETIC ACID INDUCED ULCERATIVE COLITIS IN RATS

Abstract

An eco-friendly method has been used to synthesize the novel sulfonamides from 5-aminosalicylic acid and substituted sulfonyl chlorides (3a-3e). To study the structure activity relationship (SAR), similar sulfonamides from 3-aminobenzoic acid (3f-3j) and 4-aminophenol (3k-3o) were synthesized by following the same synthetic route. All the synthesized compounds were characterized by their physical and spectral data. The compounds were evaluated for their in-vitro antioxidant properties and antibacterial activity by agar well diffusion method. The selected compounds (3a, 3b, 3k and 3l) were evaluated against acetic acid induced ulcerative colitis in rats. The present work revealed that the sulfonamides synthesized from 5-aminosalicylic acid and 4-aminophenol exhibited excellent in-vitro antioxidant properties in both DPPH and nitric oxide free radical scavenging assays. Among the 5- aminosalicylic acid sulfonamides, 3b and 3e were found more active than the standard ascorbic acid in DPPH scavenging model. The antibacterial activity data revealed that the compound 3g showed good activity towards all the tested organisms better than the standard drug sulfanilamide and with greater zone of inhibition against E.coli, S.aureus and B.subtilis when compared with the standard Amoxicillin. The pharmacological study revealed that the evaluated compounds exhibited reduced levels of colonic lipid peroxides and myeloperoxidase, while increased levels of glutathione content compared to disease control. Further, the importance of various substituents on the sulfonamide pharmacophore was supported by prediction of molecular properties and bioactivity scores using Molinspiration Cheminformatics software. The prediction data indicated that the novel compounds 3b and 3g were bioactive molecules as protease and enzyme inhibitors.