Biomaterial Database

New Adamantane-Containing Edaravone Conjugates as Potential Neuroprotective Agents for ALS Treatments. 2023

Maria A Lapshina, and Elena F Shevtsova, and Vladimir V Grigoriev, and Aleksey Yu Aksinenko, and Aleksey A Ustyugov, and Daniil A Steinberg, and Grigoriy V Maleev, and Elena S Dubrovskaya, and Tatiana V Goreva, and Tatiana A Epishina, and Vladimir L Zamoyski, and Galina F Makhaeva, and Vladimir P Fisenko, and Ivan M Veselov, and Daria V Vinogradova, and Sergey O Bachurin

Institute of Physiologically Active Compounds at the Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, 1 Severnij proezd, 142432 Chernogolovka, Russia.

Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs-edaravone and riluzole-have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone-phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077553	Edaravone	An antipyrine derivative that functions as a free radical scavenger and neuroprotective agent. It is used in the treatment of AMYOTROPHIC LATERAL SCLEROSIS and STROKE.	1-Phenyl-3-methyl-5-pyrazolone,3-Methyl-1-phenyl-2-pyrazolin-5-one,Edarabone,MCI 186,MCI-186,Norantipyrine,Norphenazone,Phenylmethylpyrazolone,Radicava,1 Phenyl 3 methyl 5 pyrazolone,3 Methyl 1 phenyl 2 pyrazolin 5 one,MCI186
D000218	Adamantane	A tricyclo bridged hydrocarbon.	Diamantane
D000547	Amantadine	An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.	1-Aminoadamantane,Adamantylamine,Adekin,Aman,Amanta,Amanta-HCI-AZU,Amanta-Sulfate-AZU,Amantadin AL,Amantadin AZU,Amantadin Stada,Amantadin-neuraxpharm,Amantadin-ratiopharm,Amantadina Juventus,Amantadina Llorente,Amantadine Hydrochloride,Amantadine Sulfate,Amixx,Cerebramed,Endantadine,Gen-Amantadine,Infecto-Flu,Infex,Mantadix,Midantan,PMS-Amantadine,Symadine,Symmetrel,Viregyt,Wiregyt,tregor,1 Aminoadamantane,AL, Amantadin,AZU, Amantadin,Amanta HCI AZU,Amanta Sulfate AZU,AmantaHCIAZU,AmantaSulfateAZU,Amantadin neuraxpharm,Amantadin ratiopharm,Amantadinneuraxpharm,Amantadinratiopharm,Gen Amantadine,GenAmantadine,Hydrochloride, Amantadine,Infecto Flu,InfectoFlu,Juventus, Amantadina,Llorente, Amantadina,PMS Amantadine,PMSAmantadine,Stada, Amantadin,Sulfate, Amantadine
D000690	Amyotrophic Lateral Sclerosis	A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)	ALS - Amyotrophic Lateral Sclerosis,Lou Gehrig Disease,Motor Neuron Disease, Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis With Dementia,Amyotrophic Lateral Sclerosis, Guam Form,Amyotrophic Lateral Sclerosis, Parkinsonism-Dementia Complex of Guam,Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex 1,Charcot Disease,Dementia With Amyotrophic Lateral Sclerosis,Gehrig's Disease,Guam Disease,Guam Form of Amyotrophic Lateral Sclerosis,Lou Gehrig's Disease,Lou-Gehrigs Disease,ALS Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis Parkinsonism Dementia Complex 1,Amyotrophic Lateral Sclerosis, Parkinsonism Dementia Complex of Guam,Disease, Guam,Disease, Lou-Gehrigs,Gehrig Disease,Gehrigs Disease,Sclerosis, Amyotrophic Lateral
D018696	Neuroprotective Agents	Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.	Neuroprotectant,Neuroprotective Agent,Neuroprotective Drug,Neuroprotectants,Neuroprotective Drugs,Neuroprotective Effect,Neuroprotective Effects,Agent, Neuroprotective,Agents, Neuroprotective,Drug, Neuroprotective,Drugs, Neuroprotective,Effect, Neuroprotective,Effects, Neuroprotective
D019782	Riluzole	A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.	2-Amino-6-trifluoromethoxybenzothiazole,PK-26124,RP-54274,Rilutek,2 Amino 6 trifluoromethoxybenzothiazole,PK 26124,PK26124,RP 54274,RP54274