Thiazolidinone-linked1,2,3-triazoles with monoterpenic skeleton as new potential anticancer agents: Design, synthesis and molecular docking studies.
Fiche publication
Date publication
juillet 2021
Journal
Bioorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MORJANI Hamid
Tous les auteurs :
Oubella A, El Mansouri AE, Fawzi M, Bimoussa A, Laamari Y, Auhmani A, Morjani H, Robert A, Riahi A, Youssef Ait Itto M
Lien Pubmed
Résumé
A novel series of 1,2,3-triazole-thiazolidinone-carvone hybrid compounds has been designed and synthesized using the copper-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC) process based on (R)-Carvone-O-propargylated 5-hydroxybenzylidene-thiazolidin-4-one derivative as starting material. All compounds were characterized and identified based on their NMR and HRMS spectroscopic data. HMBC correlations confirm that under the CuAAC reaction conditions, only the 1,4-disubstituted triazole regioisomers were formed. The targeted 1,2,3-triazole-thiazolidinone-carvone hybrids and their precursors were evaluated for their cytotoxic activity against four human cancer cell lines, including fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast carcinoma (MCF-7 and MDA-MB-231). The obtained data showed that most of these compounds have moderate anti-proliferative activity with IC values between 15.04 ± 0.71 and 42.22 ± 1.20 µM. The mechanism of action of the most active compounds 14e and 14f suggested that they induce apoptosis through caspase-3/7 activation, and the compound 14e elicited S-phase arrest, while compound 14f evoked G2/M phase blockade. The molecular docking confirmed that compounds 14e and 14f were nicely bonded with caspace-3 leading up to stable protein-ligand complexes.
Mots clés
1,2,3-Triazole, Antiproliferative activity, Apoptosis, Hybrid compounds, Molecular docking, Thiazolidinone
Référence
Bioorg Chem. 2021 Jul 20;115:105184