Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core

Méndez-Rojas, Claudio; Quiroz, Gabriel; Faúndez, Mario; Gallardo-Garrido, Carlos; Pessoa‐Mahana, C. David; Chung, Hery; Gallardo-Toledo, Eduardo; Saitz-Barria, Claudio; Araya‐Maturana, Ramiro; Kogan, Marcelo J.; Zúñiga-López, María Carolina; Iturriaga-Vásquez, Patricio; Valenzuela-Gutiérrez, Carla; Pessoa‐Mahana, Hernán

doi:10.1002/ardp.201800024

Cited by 11 publications

(2 citation statements)

References 35 publications

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“…The synthetic approach for the preparation of the target compounds 7a – o is outlined below. The reaction took place between piperazine benzoxazine derivatives 6 ( a – c ) obtained in a six-step sequence and 82–95% yields ( Scheme 1 ), with 3-indolyl tosylates 1a – c (R = H, F, Br) obtained by reported literature procedures [ 37 , 46 ] to give nine final compounds 7 ( a , b , c , g , h , i , m , n , o ) in a 42–89% yield ( Scheme 2 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

et al. 2020

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A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure–activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

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Section: Resultsmentioning

confidence: 99%

Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

et al. 2020

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“…Oxazinones and oxathiinones constitute an important class of heterocycles, which has attracted much synthetic interest owing to their potential biological activities . Benzenoid derivatives of oxazinones (benzoxazinones) exhibit various pharmaceutical activities, such as antitumor , antiviral , antithrombotic , antimycobacterial , anti‐inflammatory , antidiabetic, and hypolipidemic effects.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, and Evaluation of Antibacterial and Antioxidant Activities of Novel Benzoxazinones and Benzoxathiinones

Gholami

Asghari

Mohseni

2019

Journal of Heterocyclic Chem

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In this work, the new benzoxazinones and benzoxathiinones were synthesized from reaction of alkyl X‐phenylpropiolates and aminophenol (or 2‐mercaptophenol) in the presence of triphenylphosphine. Their antibacterial activities were studied against Gram‐positive bacteria and Gram‐negative bacteria using the disc diffusion method. The obtained results showed that these compounds are more effective against Gram‐positive bacteria than against Gram‐negative bacteria. Also, evaluation of antioxidant activity of the obtained products showed that they have high to excellent antioxidant activity (79.2–93.6%).

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Recent Studies on Heterocyclic Cholinesterase Inhibitors Against Alzheimer's Disease

Tok

2024

Chemistry & Biodiversity

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Alzheimer's disease is a progressive and neurodegenerative disease characterized by impairment in emotion, language, memory and cognitive judgment. There are many factors related to Alzheimer's disease, such as amyloid beta plaques (Aβ) due to impaired metabolism of amyloid precursor protein (APP), tau hyperphosphorylation and accumulation of neurofibrillary tangles, and disruption of the cholinergic system. Disruption of the cholinergic system responsible for cognitive function and memory processes is one of the important causes of Alzheimer's disease. Therefore, cholinesterase (acetylcholinesterase and butyrylcholinesterase) inhibitors that maintain choline (acetylcholine and butyrylcholine) levels in the synaptic gap play an important role in the symptomatic treatment of Alzheimer's disease. Numerous studies have been carried out against Alzheimer's disease involving acetylcholinesterase and butyrylcholinesterase inhibitors. However, there are very few drugs (tacrine, rivastigmine, galantamine and donepezil) approved as cholinesterase inhibitors. Therefore, cholinesterase inhibitors are needed against Alzheimer's disease. This review is focused on using heterocyclic rings that show remarkable cholinesterase inhibitory activity for Alzheimer's disease. In this review, chemical structures and structure‐activity relationships of recently reported cholinesterase inhibitors are emphasized. This review will give important ideas to medicinal chemists in the discovery and development of potent cholinesterase inhibitors in their future studies.

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Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core

Cited by 11 publications

References 35 publications

Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

Synthesis, Characterization, and Evaluation of Antibacterial and Antioxidant Activities of Novel Benzoxazinones and Benzoxathiinones

Recent Studies on Heterocyclic Cholinesterase Inhibitors Against Alzheimer's Disease

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