Discovery of a new Bcl-2 inhibitor through synthesis, anticancer activity, docking and MD simulations.
Fiche publication
Date publication
mai 2023
Journal
Journal of biomolecular structure & dynamics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MORJANI Hamid
Tous les auteurs :
Byadi S, Abdoullah B, Fawzi M, Irrou E, Ait Elmachkouri Y, Oubella A, Auhmani A, Morjani H, Labd Taha M, Robert A, Aboulmouhajir A, Ait Itto MY
Lien Pubmed
Résumé
A database of 300 compounds was virtually screened and docked against Bcl-2 protein; the stability of the best-formed complex was evaluated through Molecular dynamics, the top ten compounds with the best complexation affinities were synthesized, and their cytotoxic activity was examined. Thiazolidinone (4e) and isoxazoline (4a-d) were evaluated . For further evaluation and examination, we designed and synthesized from naturally occurring (R)-carvone and characterized it spectroscopic analysis, as well as tested for their anticancer activities towards human cancer cell lines such as HT-1080 (fibrosarcome cancer), MCF-7 and MDA-MB-231 (breast cancer) and A-549 (lung cancer) by using MTT method with Doxorubicin as standard drug. Among them, compound 4d showed the most promising anticancer activity against HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 15.59 ± 3.21 µM; 18.32 ± 2.73 µM; 17.28 ± 0.33 µM and 19.27 ± 2.73 µM respectively.Communicated by Ramaswamy H. Sarma.
Mots clés
Cancer, bcl-2 protein, cytotoxic activity, isoxazoline-thiazolidinone, molecular docking and dynamic, virtual screening
Référence
J Biomol Struct Dyn. 2023 05 31;:1-10