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Abstract

Background: Coumarins, a class of benzopyrone derivatives, are known for their diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Structural flexibility enables chemical modification to enhance therapeutic potential.
Objectives: To design, synthesize, and characterize a series of novel coumarin derivatives and evaluate their in-vitro anti-inflammatory, antioxidant, and anticancer activities, with the goal of identifying potent multitarget lead compounds.
Methods: A set of five Schiff base-linked coumarin derivatives (3a–3e) were synthesized using Pechmann condensation followed by hydrazide formation and condensation with aromatic aldehydes. The compounds were characterized via FTIR, NMR, MS, and elemental analysis. Biological evaluations included anti-inflammatory assays (albumin denaturation and COX inhibition), antioxidant assays (DPPH, ABTS, FRAP), and cytotoxicity assays (MTT) against MCF-7, HeLa, A549, and normal WI-38 cell lines. Apoptosis markers (caspase-3, DNA fragmentation) were also assessed for selected compounds.
Results: Compounds 3b (p-methoxy) and 3e (p-hydroxy) exhibited the highest anti-inflammatory activity (% inhibition > 80%) and selective COX-2 inhibition. These derivatives also showed superior antioxidant activity in DPPH and ABTS assays, with IC₅₀ values close to those of standard antioxidants. In cytotoxicity studies, 3e displayed the lowest IC₅₀ values against MCF-7 and HeLa cells, coupled with a high selectivity index, indicating promising anticancer potential. SAR analysis indicated that electron-donating groups enhance both antioxidant and anticancer properties.
Conclusion: The synthesized coumarin derivatives, particularly 3b and 3e, demonstrated potent anti-inflammatory, antioxidant, and anticancer activities. These findings support their potential as lead compounds for the development of multifunctional therapeutic agents targeting inflammation, oxidative stress, and cancer.