New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Molecules Année : 2022

New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation

Résumé

Aseries of novel 1,4-disubstituted 1,2,3-triazoles were synthesized from an (R)-carvone terminal alkyne derivative via a Cu (I)-catalyzed azide–alkyne cycloaddition reaction using CuSO4,5H2O as the copper (II) source and sodium ascorbate as a reducing agent which reduces Cu (II) into Cu (I). All the newly synthesized 1,2,3-triazoles 9a–h were fully identified on the basis of their HRMS and NMR spectral data and then evaluated for their cell growth inhibition potential by MTS assay against HT-1080 fibrosarcoma, A-549 lung carcinoma, and two breast adenocarcinoma (MCF-7 and MDA-MB-231) cell lines. Compound 9d showed notable cytotoxic effects against the HT-1080 and MCF-7 cells with IC50 values of 25.77 and 27.89 µM, respectively, while compound 9c displayed significant activity against MCF-7 cells with an IC50 value of 25.03 µM. Density functional calculations at the B3LYP/6-31G* level of theory were used to confirm the high reactivity of the terminal alkyne as a dipolarophile. Quantum calculations were also used to investigate the mechanism of both the uncatalyzed and copper (I)-catalyzed azide–alkyne cycloaddition reaction (CuAAC). The catalyzed reaction gives complete regioselectivity via a stepwise mechanism streamlining experimental observations. The calculated free-energy barriers 4.33 kcal/mol and 29.35 kcal/mol for the 1,4- and 1,5-regioisomers, respectively, explain the marked regioselectivity of the CuAAC reaction.

Domaines

Chimie organique

Dates et versions

hal-03551211 , version 1 (01-02-2022)

Identifiants

Citer

Ali Oubella, Abdoullah Bimoussa, Abdellah N’ait Oussidi, Mourad Fawzi, Aziz Auhmani, et al.. New 1,2,3-Triazoles from (R)-Carvone: Synthesis, DFT Mechanistic Study and In Vitro Cytotoxic Evaluation. Molecules, 2022, 27 (3), pp.769. ⟨10.3390/molecules27030769⟩. ⟨hal-03551211⟩
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