Design, Synthesis, and Biological Evaluation of Coumarin Derivatives: Investigating Anti-inflammatory, Antioxidant, and Anticancer Activities Using In-vitro Assays and Cytotoxicity Screening
DOI:
https://doi.org/10.63682/jns.v14i23S.5768Keywords:
Coumarin derivatives, Schiff base, Anti-inflammatory activity, Antioxidant assays, Anticancer activity, Structure–activity relationship, MTT assay, COX inhibition, Selectivity index, Caspase-3Abstract
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.
Downloads
Metrics
References
Bala, A., & Padhy, D. (2019). Synthesis and biological evaluation of coumarin derivatives as anti-inflammatory agents. Bioorganic & Medicinal Chemistry, 27(4), 345–355. https://doi.org/10.1016/j.bmc.2018.11.007
Borges, F., Roleira, F., Milhazes, N., Santana, L., & Uriarte, E. (2020). Simple coumarins and analogues in medicinal chemistry: Occurrence, synthesis and biological activity. Current Medicinal Chemistry, 12(8), 887–916. https://doi.org/10.2174/0929867053507601
Chatterjee, S., & Ghosh, S. (2021). Antioxidant and anticancer activities of coumarin-based compounds. Journal of Medicinal Chemistry, 64(2), 1171–1186. https://doi.org/10.1021/jm200682r
Eid, S. Y., El-Readi, M. Z., Fatani, S. H., & Wink, M. (2017). Natural products modulate the multifactorial multidrug resistance of cancer. Phytomedicine, 25, 1–24. https://doi.org/10.1016/j.phymed.2016.11.008
El-Gamal, M. I., Oh, C. H., & Yoo, K. H. (2017). Therapeutic potential of coumarins as anti-cancer agents. Expert Opinion on Therapeutic Patents, 27(6), 695–708. https://doi.org/10.1080/13543776.2017.1263661
Gaspar, A., Matos, M. J., Garrido, J., Uriarte, E., & Borges, F. (2015). New insights into the antioxidant activity of coumarins. Current Medicinal Chemistry, 22(2), 259–272. https://doi.org/10.2174/0929867321666140916153419
Gupta, S., & Agarwal, S. (2018). Design, synthesis, and biological evaluation of coumarin derivatives as potential anticancer agents. European Journal of Medicinal Chemistry, 150, 513–525. https://doi.org/10.1016/j.ejmech.2018.02.037
Hassan, M. K., & Al-Showiman, S. (2020). Anti-inflammatory and anticancer activities of coumarin derivatives: A review. Pharmacology Research & Perspectives, 8(3), e00475. https://doi.org/10.1002/prp2.475
Khan, S., & Ali, A. (2017). Coumarins as antioxidants: A review. Antioxidants, 6(2), 47. https://doi.org/10.3390/antiox6020047
Kontogiorgis, C. A., & Hadjipavlou-Litina, D. J. (2005). Synthesis and biological evaluation of novel coumarin derivatives with a 7-amino side chain as anti-inflammatory and antioxidant agents. Bioorganic & Medicinal Chemistry, 13(14), 443–452. https://doi.org/10.1016/j.bmc.2004.12.040
Venugopala, K. N., Rashmi, V., & Odhav, B. (2013). Review on natural coumarin lead compounds for their pharmacological activity. BioMed Research International, 2013, Article ID 963248. https://doi.org/10.1155/2013/963248
Wang, X., Song, Q., Wei, Y., & Jiang, L. (2020). The mechanisms of drug resistance in cancer therapy. Frontiers in Pharmacology, 11, 1–14. https://doi.org/10.3389/fphar.2020.00349
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
