Title:Key Chemotypes for the Rational Design of Dual AChE/BACE-1
Inhibitors
Volume: 33
Issue: 1
Author(s): Densy Davis, Daniela Trisciuzzi, Rajalakshmi Sreekumar, Maria Binu Jacob, Krishnadas Madhu*, Nicola Gambacorta, Marco Catto, Della Grace Thomas Parambi, Orazio Nicolotti*Bijo Mathew*
Affiliation:
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences
Campus, AIMS Ponekkara P. O., Kochi, Kerala, 682 041, India
- Dipartimento di Farmacia Scienze
del Farmaco, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona, 4, Bari, I-70125, Italy
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa
Vidyapeetham, AIMS Health Sciences Campus, Kochi, 682 041, India
Keywords:
Acetylcholinesterase, β-secretase-1, Alzheimer’s disease, multi-targeted ligands, structure-activity relationships, homeostasis.
Abstract: A classical one-drug-one-target approach is ineffective against diseases with a
multi-factorial pathogenesis, such as Alzheimer's disease (AD). On the other hand, multitarget
approaches can provide a higher level of pharmacological interference which can
better affect the disease network. Acetylcholinesterase (AChE), beta-site amyloid precursor
protein cleaving enzyme 1 (β-secretase, BACE-1), glycogen synthase kinase 3 beta
(GSK-3β), monoamine oxidases (MAOs), metal ions in the brain, N-methyl-D-aspartate
(NMDA) receptor, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine
receptor (H3 receptor), and phosphodiesterases (PDEs) are the main major targets of this
network whose connection are still far from being fully understood. Aware of this limitation,
we herein focus on the main chemotypes employed for AChE/BACE-1 targeting.
These include mostly bioactive compounds based on chalcones, triazines, triazoles, piperidines,
and flavonoids.
