KIT | KIT-Bibliothek | Impressum | Datenschutz

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

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

Abstract:

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI$_{50}$ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI$_{50}$ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC$_{50}$ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC$_{50}$ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC$_{50}$ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC$_{50}$ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000151907
Veröffentlicht am 26.10.2022
Originalveröffentlichung
DOI: 10.1016/j.arabjc.2022.104280
Scopus
Zitationen: 3
Web of Science
Zitationen: 3
Dimensions
Zitationen: 3
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2022
Sprache Englisch
Identifikator ISSN: 1878-5352, 1878-5379
KITopen-ID: 1000151907
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in Arabian Journal of Chemistry
Verlag Elsevier
Band 15
Heft 11
Seiten Art.-Nr.: 104280
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Vorab online veröffentlicht am 21.09.2022
Schlagwörter Huisgen cycloaddition, 1,3-Thiazolidin-4-ones, CDK2, EGFR, Diethyl azodicarboxylate
Nachgewiesen in Web of Science
Dimensions
Scopus
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft
KITopen Landing Page