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Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.
J Med Chem. 2005 Jun 30; 48(13):4444-56.JM

Abstract

In continuing research that led us to identify a new class of carbamate derivatives acting as potent (Rampa et al. J. Med. Chem. 1998, 41, 3976) and long-lasting (Rampa et al. J. Med. Chem. 2001, 44, 3810) acetylcholinesterase (AChE) inhibitors, we obtained some analogues able to simultaneously block both the catalytic and the beta-amyloid (Abeta) proaggregatory activities of AChE. The key feature of these derivatives is a 2-arylidenebenzocycloalkanone moiety that provides the ability to bind at the AChE peripheral site responsible for promoting the Abeta aggregation. The new carbamates were tested in vitro for the inhibition of both cholinesterases and also for the ability to prevent the AChE-induced Abeta aggregation. All of the compounds had AChE IC(50) values in the nanomolar range and showed the ability to block the AChE-induced Abeta aggregation, thus supporting the feasibility of this new strategy in the search of compounds for the treatment of Alzheimer's disease.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15974596

Citation

Belluti, Federica, et al. "Cholinesterase Inhibitors: Xanthostigmine Derivatives Blocking the Acetylcholinesterase-induced Beta-amyloid Aggregation." Journal of Medicinal Chemistry, vol. 48, no. 13, 2005, pp. 4444-56.
Belluti F, Rampa A, Piazzi L, et al. Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation. J Med Chem. 2005;48(13):4444-56.
Belluti, F., Rampa, A., Piazzi, L., Bisi, A., Gobbi, S., Bartolini, M., Andrisano, V., Cavalli, A., Recanatini, M., & Valenti, P. (2005). Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation. Journal of Medicinal Chemistry, 48(13), 4444-56.
Belluti F, et al. Cholinesterase Inhibitors: Xanthostigmine Derivatives Blocking the Acetylcholinesterase-induced Beta-amyloid Aggregation. J Med Chem. 2005 Jun 30;48(13):4444-56. PubMed PMID: 15974596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation. AU - Belluti,Federica, AU - Rampa,Angela, AU - Piazzi,Lorna, AU - Bisi,Alessandra, AU - Gobbi,Silvia, AU - Bartolini,Manuela, AU - Andrisano,Vincenza, AU - Cavalli,Andrea, AU - Recanatini,Maurizio, AU - Valenti,Piero, PY - 2005/6/25/pubmed PY - 2005/8/24/medline PY - 2005/6/25/entrez SP - 4444 EP - 56 JF - Journal of medicinal chemistry JO - J Med Chem VL - 48 IS - 13 N2 - In continuing research that led us to identify a new class of carbamate derivatives acting as potent (Rampa et al. J. Med. Chem. 1998, 41, 3976) and long-lasting (Rampa et al. J. Med. Chem. 2001, 44, 3810) acetylcholinesterase (AChE) inhibitors, we obtained some analogues able to simultaneously block both the catalytic and the beta-amyloid (Abeta) proaggregatory activities of AChE. The key feature of these derivatives is a 2-arylidenebenzocycloalkanone moiety that provides the ability to bind at the AChE peripheral site responsible for promoting the Abeta aggregation. The new carbamates were tested in vitro for the inhibition of both cholinesterases and also for the ability to prevent the AChE-induced Abeta aggregation. All of the compounds had AChE IC(50) values in the nanomolar range and showed the ability to block the AChE-induced Abeta aggregation, thus supporting the feasibility of this new strategy in the search of compounds for the treatment of Alzheimer's disease. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/15974596/Cholinesterase_inhibitors:_xanthostigmine_derivatives_blocking_the_acetylcholinesterase_induced_beta_amyloid_aggregation_ L2 - https://doi.org/10.1021/jm049515h DB - PRIME DP - Unbound Medicine ER -