Newly synthesized (R)-carvone-derived 1,2,3-triazoles: structural, mechanistic, cytotoxic and molecular docking studies.
Fiche publication
Date publication
mars 2021
Journal
Journal of biomolecular structure & dynamics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MORJANI Hamid
Tous les auteurs :
Hachim ME, Oubella A, Byadi S, Fawzi M, Laamari Y, Bahsis L, Aboulmouhajir A, Morjani H, Podlipnik Č, Auhmani A, Ait Itto MY
Lien Pubmed
Résumé
In the current study, natural (R)-carvone was used as starting material for the efficient synthesis of several 1,2,3-triazole derivatives. The produced products were obtained in good yields and characterized by H and C NMR and HRMS analysis. The newly synthesized monoterpenic 1,2,3-triazole and derivatives were analyzed by viability tests (MTT) for their cytotoxic activity against three human cancer cells. Product showed a medium antitumor activity, for which the IC values against selected cells HT-1080, A-549 and MCF-7 were 29.25 μM, 31.62 μM and 26.02 μM, respectively. The regioselectivity of the condensation reaction and the molecular structure of the title compounds were determined by Density Functional Theory (DFT) using B3LYP calculations at 6-311 + G(d,p) level. The orbitals HOMO and LUMO were studied to determine the electronic properties of the synthesized compounds. In addition, the global reactivity indices were used to explain the regioselectivity for the formation of compound , and the theoretical results agree well with the experimental results. Molecular docking and molecular dynamics confirmed the empirical test results and confirmed the stability of the complex during inhibition of the anti-apoptotic protein for killing cancer cells.
Mots clés
(R)-Carvone, 123-triazole, Click chemistry, DFT calculation, Molecular docking, Regioselectivity
Référence
J Biomol Struct Dyn. 2021 Mar 15;:1-14