Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi-targeted directed compounds against Alzheimer's disease.
This paper describes the synthesis and evaluation of new dihydropyrimidinone (DHPM)-derived selenoesters as potential multi-targeted agents for the treatment of Alzheimer's disease. A series of DHPM-derived selenoesters were obtained with high structural diversity through a short and modular synthetic route. The antioxidant activity was evaluated by TBARS and iron chelation assays. These compounds were also evaluated as acetylcholinesterase inhibitors (AChEi). The compounds demonstrated good antioxidant activity, since they presented excellent lipid peroxidation inhibition and good iron chelation activity. In addition, they showed acetylcholinesterase inhibition activity and some of them presented activity superior to that of the standard drug galantamine. The in silico predictions showed that the compound 1h may present a good pharmacokinetic profile. Therefore, the series of DHPM-derived selenoesters described herein displayed good potential for the development of antioxidant and anticholinesterasic agents in the search for new multi-targeted therapeutics for the treatment of Alzheimer's disease.
Laboratório de Síntese de Substâncias Bioativas de Selênio, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil(†).
Flavio A R
FAR
Barbosa
Laboratório de Síntese de Substâncias Bioativas de Selênio, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil(†).
Rômulo F S
RFS
Canto
Laboratório de Síntese de Substâncias Bioativas de Selênio, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil(†).
Sumbal
S
Saba
Laboratório de Síntese de Substâncias Bioativas de Selênio, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil(†).
Jamal
J
Rafique
Laboratório de Síntese de Substâncias Bioativas de Selênio, Centro de Ciências Físicas e Matemáticas, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil(†). Electronic address: braga.antonio@ufsc.br.
Antonio L
AL
Braga
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D004952:Esters; D016566:Organoselenium Compounds; D011744:Pyrimidinones
Alzheimer’s disease; Antioxidant; Dihydropyrimidinones; Selenium; Selenoesters