New selective acetylcholinesterase inhibitors designed from natural piperidine alkaloids

Author(s)

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

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry; v. 13, n. 13, p. 4184-4190, July 2005.
• Field of knowledge: Physical Sciences and Mathematics - Chemistry

Abstract

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)

• FAPESP's process: 98/05074-0 - Conservation and sustainable use of the plant biodiversity from the Cerrado and the Atlantic Forest: chemical diversity and prospecting for potential drugs
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants