| Autor: |
Hefny, Salma M., El-Moselhy, Tarek F., El-Din, Nabaweya, Giovannuzzi, Simone, Bin Traiki, Thamer, Vaali-Mohammed, Mansoor-Ali, El-Dessouki, Ahmed M., Yamaguchi, Koki, Sugiura, Masaharu, Shaldam, Moataz A., Supuran, Claudiu T., Abdulla, Maha-Hamadien, Eldehna, Wagdy M., Tawfik, Haytham O. |
| Zdroj: |
Journal of Medicinal Chemistry; May 2024, Vol. 67 Issue: 9 p7406-7430, 25p |
| Abstrakt: |
A dual-targeting approach is predicted to yield better cancer therapy outcomes. Consequently, a series of coumarin-based thiazoles (5a–h, 6, and 7a–e) were designed and constructed as potential carbonic anhydrase (CA) and VEGFR-2 suppressors. The inhibitory actions of the target compounds were assessed against CA isoforms IX and VEGFR-2. The assay results showed that coumarin-based thiazoles 5a, 5d, and 5ecan effectively inhibit both targets. 5a, 5d, and 5ecytotoxic effects were tested on pancreatic, breast, and prostate cancer cells (PANC1, MCF7, and PC3). Further mechanistic investigation disclosed the ability of 5eto interrupt the PANC1 cell progression in the S stage by triggering the apoptotic cascade, as seen by increased levels of caspases 3, 9, and BAX, alongside the Bcl-2 decline. Moreover, the in vivoefficacy of compound 5eas an antitumor agent was evaluated. Also, molecular docking and dynamics displayed distinctive interactions between 5eand CA IX and VEGFR-2 binding pockets. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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