Efficient Two-Step Synthesis of Novel Pyrimido[4,5-<i>d</i>] Pyrimidines with Potent Neuroprotective, Antioxidant, and A<i>β</i> Anti-Aggregation Properties
Ghada Ben Ameur,
Emna Maalej,
Helene Martin,
Anne-Sophie Jacquinot,
Nadine Barbanneau,
Paul J. Bernard,
José Marco-Contelles,
Fakher Chabchoub,
Lhassane Ismaili
Affiliations
Ghada Ben Ameur
Laboratory of Applied Chemistry, Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, B.P. 802, Sfax 3000, Tunisia
Emna Maalej
Laboratoire Matériaux, Traitement et Analyse (LMTA), Institut National de Recherche et d’Analyse Physico-Chimique (INRAP), Ariana 2020, Tunisia
Helene Martin
Université de Franche-Comté, EFS, INSERM, UMR RIGHT, F-25000 Besançon, France
Anne-Sophie Jacquinot
Université de Franche-Comté, EFS, INSERM, UMR RIGHT, F-25000 Besançon, France
Nadine Barbanneau
Université de Franche-Comté, UMR INSERM 1322 LINC, F-25000 Besançon, France
Paul J. Bernard
Université de Franche-Comté, UMR INSERM 1322 LINC, F-25000 Besançon, France
José Marco-Contelles
Laboratory of Medicinal Chemistry (IQOG, CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain
Fakher Chabchoub
Laboratory of Applied Chemistry, Heterocycles, Lipids and Polymers, Faculty of Sciences of Sfax, University of Sfax, B.P. 802, Sfax 3000, Tunisia
Lhassane Ismaili
Université de Franche-Comté, UMR INSERM 1322 LINC, F-25000 Besançon, France
Eleven new differently substituted N,7-diphenylpyrimido [4,5-d]pyrimidin-4-amines 4a–k were synthesized from readily available reagents in a simple and inexpensive two-step procedure with yields up to 57%. Neuroprotective analysis against H2O2 and analysis using ORAC assays identified compounds 4g, 4i and 4j as promising antioxidant compounds. These compounds also showed potent inhibition of Aβ1–42 self-aggregation, and suitable physicochemical properties predicted by Datawarior software V6.1.0, this biological activity and physicochemical property being of great interest for pathologies linked to oxidative stress, such as Alzheimer’s disease.
