Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights.

Eldehna, WM; Maklad, RM; Almahli, H; Al-Warhi, T; Elkaeed, EB; Abourehab, MAS; Abdel-Aziz, HA; El Kerdawy, AM

Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights.

Eldehna, WM Maklad, RM Almahli, H Al-Warhi, T Elkaeed, EB Abourehab, MAS Abdel-Aziz, HA El Kerdawy, AM

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Publisher:: TAYLOR & FRANCIS LTD
Publication Type:: Journal Article
Citation:: J Enzyme Inhib Med Chem, 2022, 37, (1), pp. 1227-1240
Issue Date:: 2022-12

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Field	Value	Language
dc.contributor.author	Eldehna, WM
dc.contributor.author	Maklad, RM
dc.contributor.author	Almahli, H
dc.contributor.author	Al-Warhi, T
dc.contributor.author	Elkaeed, EB
dc.contributor.author	Abourehab, MAS
dc.contributor.author	Abdel-Aziz, HA
dc.contributor.author	El Kerdawy, AM
dc.date.accessioned	2025-01-31T01:20:42Z
dc.date.available	2025-01-31T01:20:42Z
dc.date.issued	2022-12
dc.identifier.citation	J Enzyme Inhib Med Chem, 2022, 37, (1), pp. 1227-1240
dc.identifier.issn	1475-6366
dc.identifier.issn	1475-6374
dc.identifier.uri	http://hdl.handle.net/10453/184736
dc.description.abstract	In the current work, a hybridisation strategy was adopted between the privileged building blocks, benzofuran and piperazine, with the aim of designing novel CDK2 type II inhibitors. The hybrid structures were linked to different aromatic semicarbazide, thiosemicarbazide, or acylhydrazone tails to anchor the designed inhibitors onto the CDK2 kinase domain. The designed compounds showed promising CDK2 inhibitory activity. Compounds 9h, 11d, 11e and 13c showed potent inhibitory activity (IC50 of 40.91, 41.70, 46.88, and 52.63 nM, respectively) compared to staurosporine (IC50 of 56.76 nM). Moreover, benzofurans 9e, 9h, 11d, and 13b showed promising antiproliferative activities towards different cancer cell lines, and non-significant cytotoxicity on normal lung fibroblasts MRC-5 cell line. Furthermore, a cell cycle analysis as well as Annexin V-FITC apoptosis assay on Panc-1 cell line were performed. Molecular docking simulations were performed to explore the ability of target benzofurans to adopt the common binding pattern of CDK2 type II inhibitors.
dc.format	Print
dc.language	eng
dc.publisher	TAYLOR & FRANCIS LTD
dc.relation.ispartof	J Enzyme Inhib Med Chem
dc.relation.isbasedon	10.1080/14756366.2022.2062337
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology
dc.subject.classification	Medicinal & Biomolecular Chemistry
dc.subject.classification	3404 Medicinal and biomolecular chemistry
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Benzofurans
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	Molecular Docking Simulation
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Benzofurans
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Molecular Docking Simulation
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Benzofurans
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cell Proliferation
dc.subject.mesh	Drug Screening Assays, Antitumor
dc.subject.mesh	Molecular Docking Simulation
dc.subject.mesh	Molecular Structure
dc.subject.mesh	Protein Kinase Inhibitors
dc.subject.mesh	Structure-Activity Relationship
dc.title	Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights.
dc.type	Journal Article
utslib.citation.volume	37
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0601 Biochemistry and Cell Biology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-01-31T01:20:39Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	37
utslib.citation.issue	1

Abstract:

In the current work, a hybridisation strategy was adopted between the privileged building blocks, benzofuran and piperazine, with the aim of designing novel CDK2 type II inhibitors. The hybrid structures were linked to different aromatic semicarbazide, thiosemicarbazide, or acylhydrazone tails to anchor the designed inhibitors onto the CDK2 kinase domain. The designed compounds showed promising CDK2 inhibitory activity. Compounds 9h, 11d, 11e and 13c showed potent inhibitory activity (IC50 of 40.91, 41.70, 46.88, and 52.63 nM, respectively) compared to staurosporine (IC50 of 56.76 nM). Moreover, benzofurans 9e, 9h, 11d, and 13b showed promising antiproliferative activities towards different cancer cell lines, and non-significant cytotoxicity on normal lung fibroblasts MRC-5 cell line. Furthermore, a cell cycle analysis as well as Annexin V-FITC apoptosis assay on Panc-1 cell line were performed. Molecular docking simulations were performed to explore the ability of target benzofurans to adopt the common binding pattern of CDK2 type II inhibitors.

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http://hdl.handle.net/10453/184736