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Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma

Inhibiting Cyclin-dependent kinase 2 (CDK2) has been established as a therapeutic strategy for the treatment of many cancers. Accordingly, this study aimed at developing a new set of quinazolinone-based derivatives as CDK2 inhibitors. The new compounds were evaluated for their anticancer activity ag...

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Autores principales: Mohammed, Eman R., Elmasry, Ghada F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843100/
https://www.ncbi.nlm.nih.gov/pubmed/35139719
http://dx.doi.org/10.1080/14756366.2022.2036985
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author Mohammed, Eman R.
Elmasry, Ghada F.
author_facet Mohammed, Eman R.
Elmasry, Ghada F.
author_sort Mohammed, Eman R.
collection PubMed
description Inhibiting Cyclin-dependent kinase 2 (CDK2) has been established as a therapeutic strategy for the treatment of many cancers. Accordingly, this study aimed at developing a new set of quinazolinone-based derivatives as CDK2 inhibitors. The new compounds were evaluated for their anticancer activity against sixty tumour cell lines. Compounds 5c and 8a showed excellent growth inhibition against the melanoma cell line MDA-MB-435 with GI% of 94.53 and 94.15, respectively. Cell cycle analysis showed that compound 5c led to cell cycle cessation at S phase and G2/M phase revealing that CDK2 could be the plausible biological target. Thus, the most cytotoxic candidates 5c and 8a were evaluated in vitro for their CDK2 inhibitory activity and were able to display significant inhibitory action. The molecular docking study confirmed the obtained results. ADME study predicted that 5c had appropriate drug-likeness properties. These findings highlight a rationale for further development and optimisation of novel CDK2 inhibitors.
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spelling pubmed-88431002022-02-15 Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma Mohammed, Eman R. Elmasry, Ghada F. J Enzyme Inhib Med Chem Research Paper Inhibiting Cyclin-dependent kinase 2 (CDK2) has been established as a therapeutic strategy for the treatment of many cancers. Accordingly, this study aimed at developing a new set of quinazolinone-based derivatives as CDK2 inhibitors. The new compounds were evaluated for their anticancer activity against sixty tumour cell lines. Compounds 5c and 8a showed excellent growth inhibition against the melanoma cell line MDA-MB-435 with GI% of 94.53 and 94.15, respectively. Cell cycle analysis showed that compound 5c led to cell cycle cessation at S phase and G2/M phase revealing that CDK2 could be the plausible biological target. Thus, the most cytotoxic candidates 5c and 8a were evaluated in vitro for their CDK2 inhibitory activity and were able to display significant inhibitory action. The molecular docking study confirmed the obtained results. ADME study predicted that 5c had appropriate drug-likeness properties. These findings highlight a rationale for further development and optimisation of novel CDK2 inhibitors. Taylor & Francis 2022-02-09 /pmc/articles/PMC8843100/ /pubmed/35139719 http://dx.doi.org/10.1080/14756366.2022.2036985 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Mohammed, Eman R.
Elmasry, Ghada F.
Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma
title Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma
title_full Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma
title_fullStr Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma
title_full_unstemmed Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma
title_short Development of newly synthesised quinazolinone-based CDK2 inhibitors with potent efficacy against melanoma
title_sort development of newly synthesised quinazolinone-based cdk2 inhibitors with potent efficacy against melanoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843100/
https://www.ncbi.nlm.nih.gov/pubmed/35139719
http://dx.doi.org/10.1080/14756366.2022.2036985
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