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Design, Synthesis and Biological Evaluation of Syn and Anti-like Double Warhead Quinolinones Bearing Dihydroxy Naphthalene Moiety as Epidermal Growth Factor Receptor Inhibitors with Potential Apoptotic Antiproliferative Action

El-Sheref, Essmat M. ; Ameen, Mohamed A. ; El-Shaieb, Kamal M.; Abdel-Latif, Fathy F.; Abdel-naser, Asmaa I.; Brown, Alan B.; Bräse, Stefan 1; Fathy, Hazem M.; Ahmad, Iqrar; Patel, Harun; Gomaa, Hesham A. M.; Youssif, Bahaa G. M. ; Mohamed, Asmaa H.
1 Institut für Biologische und Chemische Systeme (IBCS), Karlsruher Institut für Technologie (KIT)


Our investigation includes the synthesis of new naphthalene-bis-triazole-bis-quinolin-2(1H)-ones 4a–e and 7a–e via Cu-catalyzed [3 + 2] cycloadditions of 4-azidoquinolin-2(1H)-ones 3a–e with 1,5-/or 1,8-bis(prop-2-yn-1-yloxy)naphthalene (2) or (6). All structures of the obtained products have been confirmed with different spectroscopic analyses. Additionally, a mild and versatile method based on copper-catalyzed [3 + 2] cycloaddition (Meldal–Sharpless reaction) was developed to tether quinolinones to O-atoms of 1,5- or 1,8-dinaphthols. The triazolo linkers could be considered as anti and syn products, which are interesting precursors for functionalized epidermal growth factor receptor (EGFR) inhibitors with potential apoptotic antiproliferative action. The antiproliferative activities of the 4a–e and 7a–e were evaluated. Compounds 4a–e and 7a–e demonstrated strong antiproliferative activity against the four tested cancer cell lines, with mean GI50 ranging from 34 nM to 134 nM compared to the reference erlotinib, which had a GI50 of 33 nM. The most potent derivatives as antiproliferative agents, compounds 4a, 4b, and 7d, were investigated for their efficacy as EGFR inhibitors, with IC50 values ranging from 64 nM to 97 nM. ... mehr

Verlagsausgabe §
DOI: 10.5445/IR/1000154519
Veröffentlicht am 13.01.2023
DOI: 10.3390/molecules27248765
Zitationen: 2
Zitationen: 2
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2022
Sprache Englisch
Identifikator ISSN: 1420-3049
KITopen-ID: 1000154519
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Molecules
Verlag MDPI
Band 27
Heft 24
Seiten Art.-Nr.: 8765
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 10.12.2022
Schlagwörter azide; naphthalene; click; quinolin-2-one; apoptosis; caspases; antiproliferative; reaction mechanism
Nachgewiesen in Dimensions
Web of Science
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