Benzylphenylpyrrolizinones with Anti-amyloid and Radical Scavenging Effects, Potentially Useful in Alzheimer's Disease Treatment.
Herein we describe the drug design steps developed to increase the radical scavenging and β-amyloid aggregation inhibitory activities of a previously described series of benzylidenephenylpyrrolizinones. Among the newly synthesized derivatives, some benzylphenylpyrrolizinones exhibited interesting results in regard to those activities. Initial druggability parameters were measured, and suggest these compounds as a suitable starting point for potential alternatives in treating Alzheimer's disease.
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Jean-Pierre
0000-0002-0553-9705
JP
Jourdan
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Marc
M
Since
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Laïla
L
El Kihel
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Cédric
0000-0003-4725-7738
C
Lecoutey
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Sophie
S
Corvaisier
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Rémi
R
Legay
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Jana
0000-0002-4829-8120
J
Sopková-de Oliveira Santos
CIBLOT, IPSIT-IFR141, 92290, Châtenay-Malabry, France.
Thierry
0000-0002-1398-5115
T
Cresteil
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Aurélie
A
Malzert-Fréon
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Christophe
0000-0001-7996-2082
C
Rochais
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ., UNICAEN, CERMN, 14000, Caen, France.
Patrick
0000-0002-4845-615X
P
Dallemagne
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D066329:Protein Aggregates / Q000187:drug effects; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D058669:Adrenergic alpha-2 Receptor Antagonists; D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D066329:Protein Aggregates; D011763:Pyrrolizidine Alkaloids
Alzheimer′s disease; MTDL; antioxidants; pyrrolizinones; β-amyloid