Novel benzo[4,5]thiazolo[2,3-C][1,2,4]triazoles: Design, synthesis, anticancer evaluation, kinase profiling and molecular docking study

Autor:	Asmaa G. Safi El-Din, Ahmed H. Abdelazeem, Ahmed M. Gouda, Alaa M. Alqahtani, Hany H. Arab
Rok vydání:	2021
Předmět:	A549 cell chemistry.chemical_classification Kinase Stereochemistry Isatin Organic Chemistry Triazole Analytical Chemistry Inorganic Chemistry chemistry.chemical_compound Enzyme chemistry Docking (molecular) Moiety Cytotoxicity Spectroscopy
Zdroj:	Journal of Molecular Structure. 1246:131138
ISSN:	0022-2860
DOI:	10.1016/j.molstruc.2021.131138
Popis:	In the current study, we report the synthesis and cytotoxic evaluation of a new series of S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole-based derivatives 8-12. Cytotoxicity of the new compounds was investigated in A549, MCF-7, and Hep3B cancer cell lines. Among these derivatives, compound 12 bearing an isatin moiety was the most active derivative (IC50 = 2.40-3.53 µM). A mechanistic study of compound 12 was performed using the kinase profiling test to explore its inhibitory activity against 10 types of the oncogenic kinases and the potential activation of caspase 3/7 enzymes. The results revealed that compound 12 showed moderate inhibition of the EGFR and LCK kinases. Moreover, compound 12 also activated caspase-3/7 in A549 cells. The docking study of compound 12 into EGFR ATP-active site revealed that it fits nicely with good binding affinity. Together, the results indicated that compound 12 could serve as a good lead for developing new potential anticancer agents.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::89d250f657ead5c55c89a02aef00bd8a https://doi.org/10.1016/j.molstruc.2021.131138 Zobrazit plný text záznamu Full Text from ScienceDirect