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

Autor: Hashem H; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt., Hassan A; Medicinal Chemistry Department, Faculty of Pharmacy, South Valley University, Qena 52242, Egypt.; Medicinal Chemistry Department, Clinical Pharmacy Program, South Valley National University, Qena 52242, Egypt., Abdelmagid WM; Medicinal Chemistry and Drug Discovery Research Centre, Swenam College, 210-6125 Sussex Avenue, Burnaby, BC V5H 4G1, Canada., Habib AGK; Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef 62521, Egypt., Abdel-Aal MAA; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt., Elshamsy AM; Medicinal Chemistry Department, Faculty of Pharmacy, Deraya University, New Minia 61768, Egypt., El Zawily A; Department of Plant and Microbiology, Faculty of Science, Damanhour University, Damanhour 22511, Egypt.; Division of Pharmaceutics and Translation Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA., Radwan IT; Supplementary General Sciences Department, Faculty of Oral and Dental Medicine, Future University in Egypt, Cairo 11835, Egypt., Bräse S; Institute of Biological and Chemical Systems-Functional Molecular Systems (IBCS-FMS), Karlsruhe Institute of Technology (KIT), Kaiserstrasse 12, 76131 Karlsruhe, Germany., Abdel-Samea AS; Pharmacology and Toxicology Department, Faculty of Pharmacy, Deraya University, New Minia 61768, Egypt., Rabea SM; Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.; Apogee Pharmaceuticals Inc., 4475 Wayburne Dr., Suite 105, Burnaby, BC V6V2H8, Canada.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 Aug 31; Vol. 17 (9). Date of Electronic Publication: 2024 Aug 31.
DOI: 10.3390/ph17091154
Abstrakt: 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 GI 50 range from 1.55 to 2.95 μΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC 50 value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC 50 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.
Databáze: MEDLINE
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