Synthesis of New Thiazole-Privileged Chalcones as Tubulin Polymerization Inhibitors with Potential Anticancer Activities

• Main Authors: Hamada Hashem (Author), Abdelfattah Hassan (Author), Walid M. Abdelmagid (Author), Ahmed G. K. Habib (Author), Mohamed A. A. Abdel-Aal (Author), Ali M. Elshamsy (Author), Amr El Zawily (Author), Ibrahim Taha Radwan (Author), Stefan Bräse (Author), Ahmed S. Abdel-Samea (Author), Safwat M. Rabea (Author)
• Format: Book
• Published: MDPI AG, 2024-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives <b>2a</b>-<b>2p</b> exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI₅₀ range from 1.55 to 2.95 μΜ, respectively. Compound <b>2e</b> demonstrated significant inhibition of tubulin polymerization, with an IC₅₀ value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC₅₀ value of 4.93 μM. Molecular docking studies of compounds <b>2e</b>, <b>2g</b>, and <b>2h</b> into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents.

Item Description

10.3390/ph17091154
1424-8247