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Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAFV600E

Synthesis and Antiproliferative Potential of Thiazole and 4-Thiazolidinone Containing Motifs as Dual Inhibitors of EGFR and BRAFV600E

Authors :
Alaa A. Hassan
Nasr K. Mohamed
Ashraf A. Aly
Mohamed Ramadan
Hesham A. M. Gomaa
Ahmed T. Abdel-Aziz
Bahaa G. M. Youssif
Stefan Bräse
Olaf Fuhr
Source :
Molecules, Vol 28, Iss 24, p 7951 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Thiazole and thiazolidinone recur in a wide range of biologically active compounds that reach different targets within the context of tumors and represent a promising starting point to access potential candidates for treating metastatic cancer. Therefore, searching for new lead compounds that show the highest anticancer potency with the fewest adverse effects is a major drug-discovery challenge. Because the thiazole ring is present in dasatinib, which is currently used in anticancer therapy, it is important to highlight the ring. In this study, cycloalkylidenehydrazinecarbothioamides (cyclopentyl, cyclohexyl, cyclooctyl, dihydronapthalenylidene, flurine-9-ylidene, and indolinonyl) reacted with 2-bromoacetophenone and diethylacetylenedicarboxylate to yield thiazole and 4-thiazolidinone derivatives. The structure of the products was confirmed by using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and single-crystal X-ray analyses. The antiproliferative activity of the newly synthesized compounds was evaluated. The most effective inhibitory compounds were further tested in vitro against both epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAFV600E) targets. Additionally, molecular docking analysis examined how these molecules bind to the active sites of EGFR and BRAFV600E.

Details

Language :
English
ISSN :
14203049
Volume :
28
Issue :
24
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.7feb057c741149129a88a88a7cb30fee
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules28247951