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In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues

The objective of this study is to evaluate a series of molecules based on cyclosulfamide as potential anticancer agents. Additionally, the study aims to analyze the obtained results through in silico studies; by conducting experiments and utilizing theoretical methods. In this context, we investigat...

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Autores principales: Bouzina, Abdeslem, Bouone, Yousra Ouafa, Sekiou, Omar, Aissaoui, Mohamed, Ouk, Tan-Sothea, Djemel, Abdelhak, Mansouri, Rachida, Ibrahim-Ouali, Malika, Bouslama, Zihad, Aouf, Nour-Eddine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10301704/
https://www.ncbi.nlm.nih.gov/pubmed/37388149
http://dx.doi.org/10.1039/d3ra02904b
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author Bouzina, Abdeslem
Bouone, Yousra Ouafa
Sekiou, Omar
Aissaoui, Mohamed
Ouk, Tan-Sothea
Djemel, Abdelhak
Mansouri, Rachida
Ibrahim-Ouali, Malika
Bouslama, Zihad
Aouf, Nour-Eddine
author_facet Bouzina, Abdeslem
Bouone, Yousra Ouafa
Sekiou, Omar
Aissaoui, Mohamed
Ouk, Tan-Sothea
Djemel, Abdelhak
Mansouri, Rachida
Ibrahim-Ouali, Malika
Bouslama, Zihad
Aouf, Nour-Eddine
author_sort Bouzina, Abdeslem
collection PubMed
description The objective of this study is to evaluate a series of molecules based on cyclosulfamide as potential anticancer agents. Additionally, the study aims to analyze the obtained results through in silico studies; by conducting experiments and utilizing theoretical methods. In this context, we investigated the cytotoxic activity of enastron analogues on three human cell lines PRI (lymphoblastic cell line) derived from B-cell lymphoma. JURKAT (ATCC TIB-152) acute T cell leukaemia and K562 (ATCC CLL-243) is a chronic myelogenous leukaemia. Most of the tested compounds showed good inhibitory activity compared with the reference ligand (chlorambucil). The 5a derivative demonstrated the strongest effect against all cancer cells used. Furthermore, molecular docking simulations of the Eg5–enastron analogue complex revealed that studied molecules have the ability to inhibit the Eg5 enzyme, as evidenced by their calculated docking score. Following the promising results from the molecular docking study, the complex Eg5–4a underwent a 100 ns molecular dynamics simulation using Desmond. During the simulation, the receptor-ligand pairing demonstrated substantial stability after the initial 70 ns. In addition, we used DFT calculations to analyze the electronic and geometric characteristics of the studied compounds. The HOMO and LUMO band gap energies, and the molecular electrostatic potential surface were also deducted for the stable structure of each compound. Also, we studied the prediction of absorption, distribution, metabolism and excretion (ADME) of the compounds.
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spelling pubmed-103017042023-06-29 In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues Bouzina, Abdeslem Bouone, Yousra Ouafa Sekiou, Omar Aissaoui, Mohamed Ouk, Tan-Sothea Djemel, Abdelhak Mansouri, Rachida Ibrahim-Ouali, Malika Bouslama, Zihad Aouf, Nour-Eddine RSC Adv Chemistry The objective of this study is to evaluate a series of molecules based on cyclosulfamide as potential anticancer agents. Additionally, the study aims to analyze the obtained results through in silico studies; by conducting experiments and utilizing theoretical methods. In this context, we investigated the cytotoxic activity of enastron analogues on three human cell lines PRI (lymphoblastic cell line) derived from B-cell lymphoma. JURKAT (ATCC TIB-152) acute T cell leukaemia and K562 (ATCC CLL-243) is a chronic myelogenous leukaemia. Most of the tested compounds showed good inhibitory activity compared with the reference ligand (chlorambucil). The 5a derivative demonstrated the strongest effect against all cancer cells used. Furthermore, molecular docking simulations of the Eg5–enastron analogue complex revealed that studied molecules have the ability to inhibit the Eg5 enzyme, as evidenced by their calculated docking score. Following the promising results from the molecular docking study, the complex Eg5–4a underwent a 100 ns molecular dynamics simulation using Desmond. During the simulation, the receptor-ligand pairing demonstrated substantial stability after the initial 70 ns. In addition, we used DFT calculations to analyze the electronic and geometric characteristics of the studied compounds. The HOMO and LUMO band gap energies, and the molecular electrostatic potential surface were also deducted for the stable structure of each compound. Also, we studied the prediction of absorption, distribution, metabolism and excretion (ADME) of the compounds. The Royal Society of Chemistry 2023-06-28 /pmc/articles/PMC10301704/ /pubmed/37388149 http://dx.doi.org/10.1039/d3ra02904b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Bouzina, Abdeslem
Bouone, Yousra Ouafa
Sekiou, Omar
Aissaoui, Mohamed
Ouk, Tan-Sothea
Djemel, Abdelhak
Mansouri, Rachida
Ibrahim-Ouali, Malika
Bouslama, Zihad
Aouf, Nour-Eddine
In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues
title In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues
title_full In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues
title_fullStr In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues
title_full_unstemmed In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues
title_short In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues
title_sort in vitro antitumor activity, molecular dynamics simulation, dft study, adme prediction, and eg5 binding of enastron analogues
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10301704/
https://www.ncbi.nlm.nih.gov/pubmed/37388149
http://dx.doi.org/10.1039/d3ra02904b
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