Aporphinoid Alkaloids Derivatives as Selective Cholinesterases Inhibitors: Biological Evaluation and Docking Study. 2020

Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
INQUISUR-CONICET, Departamento de Química, Universidad Nacional del Sur, Av. Alem 1253, 8000, Bahía Blanca, Argentina.

Alzheimer's dementia is a neurodegenerative disease that affects the elderly population and causes memory impairment and cognitive deficit. Manifestation of this disease is associated to acetylcholine decrease; thus, Cholinesterase inhibition is the main therapeutic strategy for the treatment of Alzheimer's disease. In the present study, a series of aporphinoid alkaloids were tested as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors in vitro. Alkaloids liriodenine (3) and cassythicine (10) were the best inhibitors of both cholinesterases with IC50 values lower than 10 μM. In addition, these alkaloids demonstrated better inhibition of BChE than reference drug galantamine. In addition, some alkaloids showed selective inhibition. Laurotetatine clorhydrate (13) selectively inhibit AChE over BChE. On the contrary, pachyconfine (7) interacted more efficiently with BChE active site. Molecular modelling studies were performed in order to illustrate key interactions between most active compounds and the enzymes and to explain their selectivity. These studies reveal that the benzodioxole moiety exhibits strong interactions due to hydrogen bonds that form with the Glu201 (AChE) and Tyr440 (BChE) residues, which is reflected in the IC50 values.

UI MeSH Term Description Entries
D011789 Quantum Theory The theory that the radiation and absorption of energy take place in definite quantities called quanta (E) which vary in size and are defined by the equation E Quantum Theories,Theories, Quantum,Theory, Quantum
D002091 Butyrylcholinesterase An aspect of cholinesterase (EC 3.1.1.8). Pseudocholinesterase,Benzoylcholinesterase,Butyrylthiocholinesterase
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D004593 Electrophorus A genus of fish, in the family GYMNOTIFORMES, capable of producing an electric shock that immobilizes fish and other prey. The species Electrophorus electricus is also known as the electric eel, though it is not a true eel. Eel, Electric,Electric Eel,Electrophorus electricus
D005702 Galantamine A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders. Galantamin,Galanthamine,Lycoremine,Reminyl,Galanthamine Hydrobromide,Nivalin,Nivaline,Razadyne
D006736 Horses Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest. Equus caballus,Equus przewalskii,Horse, Domestic,Domestic Horse,Domestic Horses,Horse,Horses, Domestic
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D000470 Alkaloids Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed) Alkaloid,Plant Alkaloid,Plant Alkaloids,Alkaloid, Plant,Alkaloids, Plant
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001060 Aporphines Dibenzoquinolines derived in plants from (S)-reticuline (BENZYLISOQUINOLINES).

Related Publications

Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
January 2020, Current Alzheimer research,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
February 2017, Bioorganic chemistry,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
April 2020, Molecules (Basel, Switzerland),
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
November 2012, European journal of medicinal chemistry,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
November 2019, Bioorganic chemistry,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
June 2011, Bioorganic & medicinal chemistry,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
May 2018, Molecules (Basel, Switzerland),
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
February 2021, Bioorganic chemistry,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
December 2020, Journal of enzyme inhibition and medicinal chemistry,
Valeria Cavallaro, and Ana Paula Murray, and Carlos Rodolfo Pungitore, and Lucas Joel Gutiérrez
November 2021, Bioorganic chemistry,
Copied contents to your clipboard!