New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids

Autor(es)

Viegas Jr, Cláudio ; Bolzani, Vanderlan S. ^[2] ; Pimentel, Luísa S. B. ; Castro, Newton G. ; Cabral, Rafael F. ; Costa, Rodrigo S. ; Floyd, Corinne ; Rocha, Mônica S. ; Young, Maria C. M. ; et al

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 13, n. 13, p. 4184-4190, July 2005.
• Área do conhecimento: Ciências Exatas e da Terra - Química
• Assunto(s): Alcaloides Inibidores da colinesterase Doença de Alzheimer

Resumo

Five new piperidine alkaloids were designed from natural (-)-3-O-acetyl-spectaline and (-)-spectaline that were obtained from the flowers of Senna spectabilis (sin. Cassia spectabilis, Leguminosae). Two semi-synthetic analogues (7 and 9) inhibited rat brain acetylcholinesterase, showing IC50 of 7.32 and 15.1 mu M, and were 21 and 9.5 times less potent against rat brain butyrylcholinesterase, respectively. Compound 9 (1 mg/kg, ip) was fully efficacious in reverting scopolamine-induced amnesia in mice. The two active compounds (7 and 9) did not show overt toxic effects at the doses tested in vivo. (AU)

• Processo FAPESP: 98/05074-0 - Conservação e uso sustentável da biodiversidade vegetal do Cerrado e da Mata Atlântica: diversidade química e prospecção de medicamentos potenciais
• Beneficiário: Vanderlan da Silva Bolzani
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático