Coumarin-amino acid hybrids as promising anticancer agents: design, synthesis, docking studies and CK2 inhibition.

Autor: El-Etrawy AS; Department of Chemistry, Basic Science Center, Misr University for Science and Technology (MUST) Al-Motamayez District 6th of the October City 77 Egypt.; Department of Pharmaceutical Organic Chemistry College of Pharmaceutical Science & Drug Manufacturing, Misr University for Science and Technology (MUST) Al-Motamayez District 6th of the October City 77 Egypt., Ramadan A; Department of Chemistry, Faculty of Science, Menoufia University Shebin El-Koam Egypt., Sherbiny FF; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University Cairo 11884 Egypt dr-farag-sherbiny@azhar.edu.eg., Zeid IF; Department of Chemistry, Faculty of Science, Menoufia University Shebin El-Koam Egypt., Abdel-Rahman AA; Department of Chemistry, Faculty of Science, Menoufia University Shebin El-Koam Egypt., Hawata MA; Department of Chemistry, Faculty of Science, Menoufia University Shebin El-Koam Egypt.
Jazyk: angličtina
Zdroj: RSC advances [RSC Adv] 2024 Aug 06; Vol. 14 (34), pp. 24671-24686. Date of Electronic Publication: 2024 Aug 06 (Print Publication: 2024).
DOI: 10.1039/d4ra04226c
Abstrakt: A series of mono-peptide, di-peptide and tri-peptide derivatives linked to a coumarin scaffold (5a-c, 7a-c, and 9a-c) were synthesized via the azide-coupling method from corresponding hydrazides 4, 6, and 8. These compounds were tested for anticancer activity against HepG-2, PC-3, and Hct-116 cell lines. Compounds, 7c, and 5b showed significant cytotoxicity, outperforming doxorubicin, with IC 50 values of 34.07, 16.06, and 16.02 μM for 7c and 42.16, 59.74, and 35.05 μM for 5b. Compound 7b also displayed promising results with IC 50 values of 72.13, 70.82, and 61.01 μM. Moreover, the key structural features of amino acids indicated that mono-peptide and di-peptide derivatives play a key role in increasing their anticancer activities compared with tri-peptides. In addition, the most potent compound 5b also exhibited strong CK2 kinase inhibition with an IC 50 value of 0.117 ± 0.005 μM compared with roscovetine as a control drug with an IC 50 value of 0.251 ± 0.011 μM. Finally, the binding mode of the chemical inhibitors at the active site of CK2 receptor was also investigated using a docking study which confirmed that the presence of the amino acid functionality is an important feature for anticancer activity and the synthesized compounds showed favorable ADME properties. Besides that, SAR analysis was implemented for the target compounds.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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