Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights.
Authors
Eldehna, Wagdy M
Almahli, Hadia
Al-Warhi, Tarfah
Elkaeed, Eslam B
Abourehab, Mohammed AS
Abdel-Aziz, Hatem A
El Kerdawy, Ahmed M
Publication Date
2022-12Journal Title
J Enzyme Inhib Med Chem
ISSN
1475-6366
Publisher
Informa UK Limited
Volume
37
Issue
1
Pages
1227-1240
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Eldehna, W. M., Maklad, R. M., Almahli, H., Al-Warhi, T., Elkaeed, E. B., Abourehab, M. A., Abdel-Aziz, H. A., & et al. (2022). Identification of 3-(piperazinylmethyl)benzofuran derivatives as novel type II CDK2 inhibitors: design, synthesis, biological evaluation, and in silico insights.. J Enzyme Inhib Med Chem, 37 (1), 1227-1240. https://doi.org/10.1080/14756366.2022.2062337
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.
Keywords
Kinase inhibitors, apoptotic agents, benzofuran synthesis, molecular docking, pancreatic cancer, Antineoplastic Agents, Benzofurans, Cell Line, Tumor, Cell Proliferation, Drug Screening Assays, Antitumor, Molecular Docking Simulation, Molecular Structure, Protein Kinase Inhibitors, Structure-Activity Relationship
Sponsorship
Umm Al-Qura University (22UQU4290565DSR02)
The Deanship of Scientific Research at Princess Nourah Bint Abdulrahman University (PNURSP2022R25)
Identifiers
35470754, PMC9126595
External DOI: https://doi.org/10.1080/14756366.2022.2062337
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337586
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