Meden_2020_Eur.J.Med.Chem_208_112766

Reference

Title : Structure-activity relationship study of tryptophan-based butyrylcholinesterase inhibitors - Meden_2020_Eur.J.Med.Chem_208_112766
Author(s) : Meden A , Knez D , Malikowska-Racia N , Brazzolotto X , Nachon F , Svete J , Salat K , Groselj U , Gobec S
Ref : Eur Journal of Medicinal Chemistry , 208 :112766 , 2020
Abstract :

A series of tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors was designed and synthesized. Compounds were optimized in terms of potency, selectivity, and synthetic accessibility. The crystal structure of the inhibitor 18 in complex with BChE revealed the molecular basis for its low nanomolar inhibition (IC50 = 2.8 nM). The favourable in vitro results enabled a first-in-animal in vivo efficacy and safety trial, which demonstrated a positive impact on fear-motivated and spatial long-term memory retrieval without any concomitant adverse motor effects. Altogether, this research culminated in a handful of new lead compounds with promising potential for symptomatic treatment of patients with Alzheimers disease.

PubMedSearch : Meden_2020_Eur.J.Med.Chem_208_112766
PubMedID: 32919297
Gene_locus related to this paper: human-BCHE

Related information

Inhibitor 6XTA-cpd18
Gene_locus human-BCHE
Structure 6XTA

Citations formats

Meden A, Knez D, Malikowska-Racia N, Brazzolotto X, Nachon F, Svete J, Salat K, Groselj U, Gobec S (2020)
Structure-activity relationship study of tryptophan-based butyrylcholinesterase inhibitors
Eur Journal of Medicinal Chemistry 208 :112766

Meden A, Knez D, Malikowska-Racia N, Brazzolotto X, Nachon F, Svete J, Salat K, Groselj U, Gobec S (2020)
Eur Journal of Medicinal Chemistry 208 :112766