Issue 28, 2023

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

Abstract

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
02 mai 2023
Accepted
16 jun 2023
First published
28 jun 2023
This article is Open Access
Creative Commons BY license

RSC Adv., 2023,13, 19567-19584

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

A. Bouzina, Y. O. Bouone, O. Sekiou, M. Aissaoui, T. Ouk, A. Djemel, R. Mansouri, M. Ibrahim-Ouali, Z. Bouslama and N. Aouf, RSC Adv., 2023, 13, 19567 DOI: 10.1039/D3RA02904B

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