Novel phthalamide derivatives as antihypertensive agents: rapid and clean synthesis, in silico and in vivo evaluation

Andrade‐Jorge, Erik; Rodriguez, Jessica; Bribiesca-Carlos, José; Gallardo‐Ortíz, Itzell A.; Trujillo‐Ferrara, José G.; Villalobos‐Molina, Rafael

doi:10.1007/s00044-019-02327-3

Cited by 3 publications

(2 citation statements)

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“…Rotational bonds, degree of torsional freedom, atomic partial loads, and non‐polar hydrogen bonds were added and analyzed with AutoDock 1.5.6 tools [35] . Molecular docking was programmed with AutoDock 1.5.6 tools and Raccoon, [36] utilizing a hybrid Lamarckian genetic algorithm [37] with an initial population of 100 randomly placed individuals, as described in our previous reports [24,29,30,38,39] . The enzyme was assigned Kollmann partial charges, and ligands were assigned Gasteiger charges.…”

Section: Methodsmentioning

confidence: 99%

“…[35] Molecular docking was programmed with AutoDock 1.5.6 tools and Raccoon, [36] utilizing a hybrid Lamarckian genetic algorithm [37] with an initial population of 100 randomly placed individuals, as described in our previous reports. [24,29,30,38,39] The enzyme was assigned Kollmann partial charges, and ligands were assigned Gasteiger charges. The grid parameters for EeAChE were 60 Å per side, with the center at X = 42.27, Y = 66.809, and Z =-81.47, and a mesh separation of 0.375 Å.…”

Section: Dockingmentioning

confidence: 99%

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Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Coaviche‐Yoval,

Tovar‐Miranda,

Rodríguez

et al. 2024

ChemMedChem

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Alzheimer’s disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. It is characterized by a progressive decline in cholinergic neurotransmission. During the development of AD, acetylcholinesterase (AChE) binds to β‐amyloid peptides to form amyloid fibrils, which aggregate into plaque deposits. These complexes are cytotoxic for the brain, causing impairment of memory, attention, and cognition. AChE inhibitors are the main treatment for AD, but their effect is only palliative. This study aimed to design and synthesize novel benzofuran derivatives and evaluate their inhibition of AChE in vitro and in silico. Results: The seven synthesized benzofuran derivatives inhibited AChE in vitro. Benzofurans hydroxy ester 4, amino ester 5, and amido ester (±)‐7 had the lowest inhibition constant (Ki) values and displayed good affinity for EeAChE in molecular docking. Six derivatives showed competitive inhibition, while the best compound (5: Ki = 36.53 mM) exhibited uncompetitive inhibition. The amino, hydroxyl, amide, and ester groups of the ligands favored interaction with the enzyme by hydrogen bonds. Conclusion: Three benzofurans were promising AChE inhibitors with excellent Ki values. In future research on their their application to AD, 5 will be considered as the base structure.

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Section: Methodsmentioning

confidence: 99%

Section: Dockingmentioning

confidence: 99%

Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Coaviche‐Yoval,

Tovar‐Miranda,

Rodríguez

et al. 2024

ChemMedChem

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Phthalamide derivatives as ACE/AChE/BuChE inhibitors against cardiac hypertrophy: an in silico, in vitro, and in vivo modeling approach

et al. 2021

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Synthesis, in silico, and evaluation of AChE inhibitory activity of N-phthaloylphenylglycine derivatives as potential anti-Alzheimer’s agents

Andrade-Jorge,

Reyes-Vallejo,

Contreras-Cruz

et al. 2023

Med Chem Res

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Mental illnesses are one of the most relevant health problems today, among which Alzheimer’s disease (AD) stands out. This is a severe disease that entails different alterations such as chronic cognitive impairment. Commercial therapy drugs have not had the expected success due to their notable and rapid pharmacological efficacy reduction, therefore, we aimed to find new compounds capable of stopping the progression of this disease by cholinesterase inhibition. We synthesized and evaluated nine new racemic compounds (two precursors and their corresponding pyrrolo[2,1-a]isoindol-5-ones with different substituents) derived from phenylglycine as potential acetylcholinesterase inhibitors. Three of them (rac-4, rac-5, and rac-6) showed good enzyme inhibition (Ki 117.5, 90.62, and 77.30 µM, respectively), with a pattern of competitive inhibition type supported by in silico and in vitro experiments, being the rac-6 derivative the best inhibitor. The structural analysis showed that the presence of the ethyl ester group in the structure favors inhibition, likewise, the presence of double bonds increases the affinity of the inhibitor for the enzyme, so these new pyrrolo[2,1-a]isoindol-5-ones derivatives might be helpful for the treatment of Alzheimer’s disease.

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Novel phthalamide derivatives as antihypertensive agents: rapid and clean synthesis, in silico and in vivo evaluation

Cited by 3 publications

References 44 publications

Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Benzofurans as Acetylcholinesterase Inhibitors for Treating Alzheimer's Disease: Synthesis, in vitro Testing, and in silico Analysis

Phthalamide derivatives as ACE/AChE/BuChE inhibitors against cardiac hypertrophy: an in silico, in vitro, and in vivo modeling approach

Synthesis, in silico, and evaluation of AChE inhibitory activity of N-phthaloylphenylglycine derivatives as potential anti-Alzheimer’s agents

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