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Synthesis of novel amidines via one-pot three component reactions: Selective topoisomerase I inhibitors with antiproliferative properties

El-Sheref, Essmat M. ; Tawfeek, Hendawy N.; Hassan, Alaa A.; Bräse, S. 1; Elbastawesy, Mohammed A. I.; Gomaa, Hesham A. M.; Mostafa, Yaser A.; Youssif, Bahaa G. M.
1 Institut für Biologische und Chemische Systeme (IBCS), Karlsruher Institut für Technologie (KIT)

Abstract:

Novel series of amidines were synthesized via the interaction between alicyclic amines, cyclic ketones, and a highly electrophilic 4-azidoquinolin-2(1H)-ones without any catalyst or additive. All the obtained products were elucidated based on NMR spectroscopy, mass spectrometry, and elemental analysis. The reaction conditions were optimized using cyclohexanone (2), piperidine (3a), and 4-azido-quinolin-2(1H)-one (1a) under an air atmosphere. The new compounds 4a-l and 5a-c were tested for antiproliferative activity against four cancer cell lines using doxorubicin as a reference drug. The most potent derivatives were compounds 4b, 4d, 4e, 4i, and 5c, with GI$_{50}$ ranging from 1.00 µM to 1.50 µM. Compound 5c was the most effective derivative against the four cancer cell lines, outperforming doxorubicin. The compounds 4b, 4d, 4e, 4i, and 5c were studied further as topoisomerase I and IIα inhibitors. The compounds tested showed selective inhibition of topo I over topo IIα. Finally, docking studies explain why these compounds prefer topo I over topo IIα.


Verlagsausgabe §
DOI: 10.5445/IR/1000153766
Veröffentlicht am 15.12.2022
Originalveröffentlichung
DOI: 10.3389/fchem.2022.1039176
Scopus
Zitationen: 2
Web of Science
Zitationen: 1
Dimensions
Zitationen: 1
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2022
Sprache Englisch
Identifikator ISSN: 2296-2646
KITopen-ID: 1000153766
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Frontiers in Chemistry
Verlag Frontiers Media SA
Band 10
Seiten Art.-Nr.: 1039176
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 18.11.2022
Schlagwörter one-pot 3CR, 4-azido-quinolin-2(1H)-ones, topo, antiproliferative, viability, heterocycles, cancer
Nachgewiesen in Web of Science
Dimensions
Scopus
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