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

Author:

Hashem Hamada1ORCID,Hassan Abdelfattah23,Abdelmagid Walid M.4,Habib Ahmed G. K.5ORCID,Abdel-Aal Mohamed A. A.6,Elshamsy Ali M.7,El Zawily Amr89,Radwan Ibrahim Taha10,Bräse Stefan11ORCID,Abdel-Samea Ahmed S.12,Rabea Safwat M.1314

Affiliation:

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.

Publisher

MDPI AG

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