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Design, synthesis, and biological evaluation of novel quinoline-based EGFR/HER-2 dual-target inhibitors as potential anti-tumor agents

Al-Wahaibi, Lamya H.; El-Sheref, Essmat M.; Tawfeek, Hendawy N.; Abou-Zied, Hesham A.; Rabea, Safwat M.; Bräse, Stefan 1; Youssif, Bahaa G. M.
1 Institut für Biologische und Chemische Systeme (IBCS), Karlsruher Institut für Technologie (KIT)

Abstract:

Dual targeting of EGFR and HER2 is a valid anti-cancer approach for treating solid tumors. We designed and synthesized a new series of EGFR/HER-2 dual-target inhibitors based on quinoline derivatives. The structure of the newly synthesized compounds was verified using 1H NMR,13C NMR, and elemental analysis. The targeted compounds were tested for antiproliferative efficacy against four cancer cell lines. All the compounds had GI50s ranging from 25 to 82 nM, with breast (MCF-7) and lung (A-549) cancer cell lines being the most sensitive. Compound 5a demonstrated the most significant antiproliferative action. With inhibitory (IC50) values of 71 and 31 nM, respectively, compound 5a proved to be the most effective dual-target inhibitor of EGFR and HER-2, outperforming the reference erlotinib (IC50 = 80 nM) as an EGFR inhibitor but falling short of the clinically used agent lapatinib (IC50 = 26 nM) as a HER2 inhibitor. The apoptotic potential activity of 5a was examined, and the findings demonstrated that 5a promotes apoptosis by activating caspase-3, 8, and Bax while simultaneously reducing the expression of the antiapoptotic protein Bcl-2. ... mehr

Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 10.2024
Sprache Englisch
Identifikator ISSN: 2046-2069
KITopen-ID: 1000176844
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in RSC Advances
Verlag Royal Society of Chemistry (RSC)
Band 14
Heft 45
Seiten 32978 – 32991
Vorab online veröffentlicht am 21.10.2024
Nachgewiesen in Dimensions
Scopus
Web of Science
Globale Ziele für nachhaltige Entwicklung Ziel 3 – Gesundheit und Wohlergehen

Verlagsausgabe §
DOI: 10.5445/IR/1000176844
Veröffentlicht am 03.12.2024
Seitenaufrufe: 12
seit 03.12.2024
Downloads: 6
seit 11.12.2024
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