DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL SUBSTITUTED CINNAMAMIDES OF 5-AMINO SALICYLIC ACID
5-Aminosalicylic acid (5-ASA), known as mesalamine, is commonly used to treat various inflammatory conditionssuch as ulcerative colitis (UC), Crohn’s disease (CD) and inflammatory bowel disease (IBD). Previous researchhasshown that the cinnamic acid and its derivatives are safe, effective and possess significant anti-inflammatory activity. Hence, the current work focuses on the preparation of some novel derivatives of 5-ASA by conjugating it withvarious substituted cinnamic acids through amide linkage. The compounds were characterised by physical andspectral data and were evaluated for in vitro antioxidant activity and anti-inflammatory activity. In-silico studieswere performed to assess the drug-likeliness, anti-inflammatory activity and toxicity of the compounds using onlinecomputational tools. Compounds 6g (3, 4, 5- OCH3), and 6e (4-OCH₃) showed strong antioxidant potential, while6g (3,4,5-OCH3), 6b (4-Cl), 6c (4-F) and 6i (4-CH(CH₃)₂) exhibited excellent anti-inflammatory effects. All derivatives complied with Lipinski’s rule, suggesting good oral bioavailability and PASS/OSIRIS analyses indicatedsignificant predicted anti-inflammatory activity with low toxicity risk. Compounds 6g, 6b, 6c and 6i emergedaspromising lead candidates for the development of safe and effective anti-inflammatory agents.
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