Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking

In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver)....

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Autores principales:	Samar S. Fatahala, Amira I. Sayed, Shahenda Mahgoub, Heba Taha, Mohamed-I kotb El-Sayed, Mohamed F. El-Shehry, Samir M. Awad, Rania H. Abd El-Hameed
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	sulfonamides cytotoxicity apoptosis cell cycle CDK2 molecular docking Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/63844fd2388340769768021dee2ea91e
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spelling	oai:doaj.org-article:63844fd2388340769768021dee2ea91e2021-11-11T17:22:30ZSynthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking10.3390/ijms2221119571422-00671661-6596https://doaj.org/article/63844fd2388340769768021dee2ea91e2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11957https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds <b>6b,d</b>–<b>g</b>, and <b>7b</b> showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound <b>6e</b> displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, <b>6e</b> was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound <b>6e</b> endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.Samar S. FatahalaAmira I. SayedShahenda MahgoubHeba TahaMohamed-I kotb El-SayedMohamed F. El-ShehrySamir M. AwadRania H. Abd El-HameedMDPI AGarticlesulfonamidescytotoxicityapoptosiscell cycleCDK2molecular dockingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11957, p 11957 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sulfonamides cytotoxicity apoptosis cell cycle CDK2 molecular docking Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	sulfonamides cytotoxicity apoptosis cell cycle CDK2 molecular docking Biology (General) QH301-705.5 Chemistry QD1-999 Samar S. Fatahala Amira I. Sayed Shahenda Mahgoub Heba Taha Mohamed-I kotb El-Sayed Mohamed F. El-Shehry Samir M. Awad Rania H. Abd El-Hameed Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking
description	In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds <b>6b,d</b>–<b>g</b>, and <b>7b</b> showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound <b>6e</b> displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, <b>6e</b> was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound <b>6e</b> endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.
format	article
author	Samar S. Fatahala Amira I. Sayed Shahenda Mahgoub Heba Taha Mohamed-I kotb El-Sayed Mohamed F. El-Shehry Samir M. Awad Rania H. Abd El-Hameed
author_facet	Samar S. Fatahala Amira I. Sayed Shahenda Mahgoub Heba Taha Mohamed-I kotb El-Sayed Mohamed F. El-Shehry Samir M. Awad Rania H. Abd El-Hameed
author_sort	Samar S. Fatahala
title	Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking
title_short	Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking
title_full	Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking
title_fullStr	Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking
title_full_unstemmed	Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking
title_sort	synthesis of novel 2-thiouracil-5-sulfonamide derivatives as potent inducers of cell cycle arrest and cdk2a inhibition supported by molecular docking
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/63844fd2388340769768021dee2ea91e
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Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking

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