Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: design, structure determination, anticancer evaluation and in silico studies

Hashem, Heba E., Amr, Abd El-Galil E., Almehizia, Abdulrahman A., Naglah, Ahmed M., Kariuki, Benson M. ORCID: https://orcid.org/0000-0002-8658-3897, Eassa, Heba A. and Nossier, Eman S. 2023. Nanoparticles of a pyrazolo-pyridazine derivative as potential EGFR and CDK-2 inhibitors: design, structure determination, anticancer evaluation and in silico studies. Molecules 28 (21) , 7252. 10.3390/molecules28217252

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Abstract

The strategic planning of this study is based upon using the nanoformulation method to prepare nanoparticles 4-SLNs and 4-LPHNPs of the previously prepared 4,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-3-amine (4) after confirming its structure with single crystal X-ray analysis. These nanoparticles exhibited promising cytotoxic activity against HepG-2, HCT-116 and MCF-7 cancer cell lines in comparison with the reference doxorubicin and the original derivative 4. Moreover, their inhibitory assessment against EGFR and CDK-2/cyclin A2 displayed improved and more favorable impact than the parent 4 and the references. Detection of their influence upon cancer biomarkers revealed upregulation of Bax, p53 and caspase-3 levels and downregulation of Bcl-2 levels. The docking simulation demonstrated that the presence of the pyrazolo[3,4-c]pyridazin-3-amine scaffold is amenable to enclosure and binding well within EGFR and CDK-2 receptors through different hydrophilic interactions. The pharmacokinetic and physicochemical properties of target 4 were also assessed with ADME investigation, and the outcome indicated good drug-like characteristics.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Chemistry
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	MDPI
Date of First Compliant Deposit:	8 November 2023
Date of Acceptance:	28 September 2023
Last Modified:	08 Nov 2023 10:15
URI:	https://orca.cardiff.ac.uk/id/eprint/163714

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