Design and Synthesis of Coumarin Derivatives as Cytotoxic Agents through PI3K/AKT Signaling Pathway Inhibition in HL60 and HepG2 Cancer Cells
oleh: Safaa M. Kishk, Enas E. Eltamany, Mohamed S. Nafie, Roaa M. Khinkar, Rawan H. Hareeri, Sameh S. Elhady, Asmaa S. A. Yassen
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-10-01 |
Deskripsi
In this study, a series of coumarin derivatives, either alone or as hybrids with cinnamic acid, were synthesized and evaluated for their cytotoxicity against a panel of cancer cells using the MTT assay. Then, the most active compounds were inspected for their mechanism of cytotoxicity by cell-cycle analysis, RT-PCR, DNA fragmentation, and Western blotting techniques. Cytotoxic results showed that compound (<b>4</b>) had a significant cytotoxic effect against HL60 cells (IC<sub>50</sub> = 8.09 µM), while compound (<b>8b</b>) had a noticeable activity against HepG2 cells (IC<sub>50</sub> = 13.14 µM). Compounds (<b>4</b>) and (<b>8b</b>) mediated their cytotoxicity via PI3K/AKT pathway inhibition. These results were assured by molecular docking studies. These results support further exploratory research focusing on the therapeutic activity of coumarin derivatives as cytotoxic agents.