Tacrine based human cholinesterase inhibitors: synthesis of peptidic-tethered derivatives and their effect on potency and selectivity

Stefania Butini; Egeria Guarino; Giuseppe Campiani; Margherita Brindisi; Salvatore Sanna Coccone; Isabella Fiorini; Ettore Novellino; Tatyana Belinskaya; Ashima Saxena; Sandra Gemma

doi:10.1016/j.bmcl.2008.08.076

Tacrine based human cholinesterase inhibitors: synthesis of peptidic-tethered derivatives and their effect on potency and selectivity

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5213-6. doi: 10.1016/j.bmcl.2008.08.076. Epub 2008 Aug 26.

Authors

Stefania Butini¹, Egeria Guarino, Giuseppe Campiani, Margherita Brindisi, Salvatore Sanna Coccone, Isabella Fiorini, Ettore Novellino, Tatyana Belinskaya, Ashima Saxena, Sandra Gemma

Affiliation

¹ European Research Centre for Drug Discovery and Development (NatSynDrugs), Via Aldo Moro 2, 53100 Siena, Italy.

PMID: 18786825
DOI: 10.1016/j.bmcl.2008.08.076

Abstract

Tacrine based reversible inhibitors of cholinesterases (ChEIs) containing peptidic tethers were synthesized to interact with specific regions at the gorge level, and their potency was determined with human (h) acetylcholinesterase and butyrylcholinesterase. Analogues 3i,j and 3l,m were identified as promising hits and may pave the way for the development of a new series of tacrine based enzyme selective hChEIs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism
Butyrylcholinesterase / metabolism
Cholinesterase Inhibitors* / chemical synthesis
Cholinesterase Inhibitors* / chemistry
Cholinesterase Inhibitors* / pharmacology
Combinatorial Chemistry Techniques
Drug Design
Humans
Molecular Structure
Peptides / chemical synthesis*
Peptides / chemistry
Peptides / pharmacology*
Structure-Activity Relationship
Tacrine* / analogs & derivatives
Tacrine* / chemical synthesis
Tacrine* / chemistry
Tacrine* / pharmacology

Substances

Cholinesterase Inhibitors
Peptides
Tacrine
Acetylcholinesterase
Butyrylcholinesterase