Mohamed A. Belkacem, Hichem B. Jannet*, Hicham Ferhout, Laila Mzali and Jalloul Bouajila* Pages 744 - 752 ( 9 )
Background: 2,5-Diketopiperazine derivatives are considered to be an important classe of cyclic peptides due to their wide range of biological activities.
Objectives: Synthesis of a new series of protected 2,5-diketopiperazine derivatives and evaluation of their in vitro biological activities.
Methods: A series of new mono-protected arylidene 2,5-diketopiperazine derivatives 3a-p have been prepared via Claisen-Schmidt condensation of the N,N-diacetyl-diketopiperazine 1 with a series of substituted arylaldehydes. All prepared compounds were characterized by 1D and 2D 1H/13C NMR and ESI-HRMS, and screened for their in vitro acetylcholenesterase, xanthine oxidase and α-amylase inhibition and cytotoxic (HCT-116, MCF-7 and OVCAR-3) activity.
Results: Among these compounds, the greatest activity against the α-amylase enzyme (percentage of inhibition (PI)=57.8±1.9%) was obtained for compound 3f bearing a phenoxy moiety. Moreover, the results demonstrated that some arylidene 2,5-diketopiperazines 3 exhibited significant cytotoxic activity against the three cell lines used. The compound 3g (4-PhCH2O.Ph) was found to be the most cytotoxic against the HCT-116, MCF-7 and OVCAR-3 cell lines (PI=83.2±2.4, 89.6±4.9 and 74.4±5.2%, respectively) followed by 3m (2-Br-5-F.Ph) then 3j (4-C2H5-3-NO2.Ph) which displayed a good cytotoxic potential against OVCAR-3 (PI=77.0±2.1 and 71.4±0.9%, respectively).
Conclusion: A series of sixteen new arylidene diketopiperazines 3a-p were synthesized via Claisen-Schmidt condensation. Most of the piperazines 3a-p exhibited a good cytotoxic and antidiabetic effects.
Synthesis, 2, 5-diketopiperazines, Claisen-Schmidt reaction, anti-acetylcholinesterase, anti-xanthine oxidase, anti-α- amylase, cytotoxic activity.
Universite de Toulouse, Universite Paul-Sabatier, Faculte de pharmacie de Toulouse, Laboratoire des IMRCP, UMR CNRS 5623, F-31062 Toulouse, Laboratoire de Chimie Heterocyclique, Produits Naturels et Reactivite, Equipe Chimie Medicinale et Produits Naturels (LR11ES39), Departement de Chimie, Faculte des Sciences de Monastir, Universite de Monastir, 5019 Monastir, Agronutrition Rue Pierre et Marie Curie immeuble BIOSTEP 31670 Labege, Agronutrition Rue Pierre et Marie Curie immeuble BIOSTEP 31670 Labege, Universite de Toulouse, Universite Paul-Sabatier, Faculte de pharmacie de Toulouse, Laboratoire des IMRCP, UMR CNRS 5623, F-31062 Toulouse