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

Hamada Hashem; Abdelfattah Hassan; Walid M Abdelmagid; Ahmed G K Habib; Mohamed A A Abdel-Aal; Ali M Elshamsy; Amr El Zawily; Ibrahim Taha Radwan; Stefan Bräse; Ahmed S Abdel-Samea; Safwat M Rabea

doi:10.3390/ph17091154

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

Pharmaceuticals (Basel). 2024 Aug 31;17(9):1154. doi: 10.3390/ph17091154.

Authors

Hamada Hashem¹, Abdelfattah Hassan^{2

3}, Walid M Abdelmagid⁴, Ahmed G K Habib⁵, Mohamed A A Abdel-Aal⁶, Ali M Elshamsy⁷, Amr El Zawily^{8

9}, Ibrahim Taha Radwan¹⁰, Stefan Bräse¹¹, Ahmed S Abdel-Samea¹², Safwat M Rabea^{13

14}

Affiliations

¹ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt.
² Medicinal Chemistry Department, Faculty of Pharmacy, South Valley University, Qena 52242, Egypt.
³ Medicinal Chemistry Department, Clinical Pharmacy Program, South Valley National University, Qena 52242, Egypt.
⁴ Medicinal Chemistry and Drug Discovery Research Centre, Swenam College, 210-6125 Sussex Avenue, Burnaby, BC V5H 4G1, Canada.
⁵ Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62521, Egypt.
⁶ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt.
⁷ Medicinal Chemistry Department, Faculty of Pharmacy, Deraya University, New Minia 61768, Egypt.
⁸ Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt.
⁹ Division of Pharmaceutics and Translation Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
¹⁰ Supplementary General Sciences Department, Faculty of Oral and Dental Medicine, Future University in Egypt, Cairo 11835, Egypt.
¹¹ Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany.
¹² Pharmacology and Toxicology Department, Faculty of Pharmacy, Deraya University, New Minia 61768, Egypt.
¹³ Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
¹⁴ Apogee Pharmaceuticals Inc., 4475 Wayburne Dr., Suite 105, Burnaby, BC V6V2H8, Canada.

Abstract

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 2a-2p 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 2e 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 2e, 2g, and 2h 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.

Keywords: anticancer; colchicine binding site; thiazole chalcones; tubulin inhibitors.

Grants and funding

This research received no external funding.