Potential of triazines in Alzheimer's disease: A versatile privileged scaffold

Gharat, Ruchita; Prabhu, A. Antony Muthu; Khambete, Mihir

doi:10.1002/ardp.202100388

Cited by 10 publications

(10 citation statements)

References 69 publications

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“…Alzheimer’s disease is a progressive neurodegenerative condition associated with characteristic pathological changes in areas of the human brain responsible for cognition [ 6 ]. Alzheimer’s disease is characterized by an abnormal accumulation of extracellular amyloid β, which forms senile plaques and intracellular neurofibrillary tangles [ 7 ].…”

Section: Epidemiology Of Alzheimer’s Diseasementioning

confidence: 99%

A Review of the Current Status of Disease-Modifying Therapies and Prevention of Alzheimer’s Disease

Parums

2024

Med Sci Monit

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Alzheimer’s disease is the most common form of dementia and includes cognitive, personality, and behavioral changes. The 2024 report from the Alzheimer’s Association estimated that 6.9 million adults >65 years in the US are currently living with Alzheimer’s disease. Modeling studies predict that this number will double by 2050, and associated healthcare costs will reach $1 trillion. In June 2021, regulatory approval of aducanumab, a humanized recombinant monoclonal antibody to amyloid β, initially raised expectations for improved disease-modifying therapy. However, in February 2024, production of aducanumab and a post-marketing clinical trial ceased in the US due to the costs and limitations of aducanumab therapy. In March 2024, biobank data identified significant modifiable risk factors for Alzheimer’s disease, including diabetes mellitus, exposure to nitrogen dioxide (a proxy for air pollution), and the frequency of alcohol intake. Therefore, modification of identifiable risk factors, combined with testing for disease-susceptibility genes, could be the most effective approach to reduce the incidence. This article aims to review the current status of disease-modifying therapies and prevention of Alzheimer’s disease.

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Section: Epidemiology Of Alzheimer’s Diseasementioning

confidence: 99%

A Review of the Current Status of Disease-Modifying Therapies and Prevention of Alzheimer’s Disease

Parums

2024

Med Sci Monit

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“…1,3,5‐Triazine is a six‐membered aromatic ring compound containing three nitrogen atoms which possesses a wide range of biological activities such as anti‐inflammatory, antimicrobial, anticancer, antiviral, and antimalarial [20–28] . Numerous 1.3,5‐triazine‐containing molecules are capable of modulating single as well as multiple pathological factors involved in AD due to the potential for multiple biological effects of 1.3,5‐triazine [29] . 1,3,5‐Triazine hybrid compounds have been developed as multi‐target ligands against Alzheimer's disease [30] .…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22][23][24][25][26][27][28] Numerous 1.3,5triazine-containing molecules are capable of modulating single as well as multiple pathological factors involved in AD due to the potential for multiple biological effects of 1.3,5-triazine. [29] 1,3,5-Triazine hybrid compounds have been developed as multi-target ligands against Alzheimer's disease. [30] Some of the 1,3,5-triazine derivatives were designed and synthesized as AChE inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

Zhang,

Wang,

Zou

et al. 2024

ChemistrySelect

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A series of coumarin‐1,3,5‐triazine derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. The structures of those compounds were characterized by IR, NMR, HRMS, HPLC, and X‐ray. The structures of those coumarin‐1,3,5‐triazine derivatives are the mixtures of two geometric isomers. The 1H‐NMR of compound 3 g without coumarin structure and its hydrochloride and single crystal structure of compound 3 g were studied to prove the coumarin‐1,3,5‐triazine derivatives are the mixtures of two geometric isomers. The acetylcholinesterase and butyrylcholinesterase inhibitory activities of the synthesized compounds were determinated by Ellman's method. The results showed that all the compounds could inhibit acetylcholinesterase selectively. Among them, compound 3 b was found to have the strongest inhibitory effect on acetylcholinesterase with an IC50 value of 0.018 μM, which was closest to the IC50 of the positive control donepezil (IC50=0.016 μM). Enzyme kinetic studies indicate that this compound inhibited acetylcholinesterase with a mixed mode. Molecular docking, molecular dynamics simulation study and binding free energy calculation experiments demonstrated that compound 3 b could stably interact with key amino acids in the catalytically active site and the peripheral anion site of acetylcholinesterase. According to the results, compound 3 b demonstrates promising potential as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

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“…Triazines have been explored in drug discovery programs owing to their stability in biological media and robust reactivity. Their unique chemical properties have led to the exploration of the triazine containing molecules for AD [26] . Some derivatives of 1,3,5‐triazine have been proved to be a kind of effective AChE inhibitors [27,28] .…”

Section: Introductionmentioning

confidence: 99%

“…Their unique chemical properties have led to the exploration of the triazine containing molecules for AD. [26] Some derivatives of 1,3,5-triazine have been proved to be a kind of effective AChE inhibitors. [27,28] Our previous work has developed a series of 1,3,5-triazine derivatives as multifunctional AChE inhibitors [29] and a 7-O-modified genistein derivative with AChE inhibitory effect, estrogenic activity and neuroprotective effect.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Biological Evaluation and Molecular Dynamics Simulations Study of Genistein‐O‐1,3,5‐Triazine Derivatives as Multifunctional Anti‐Alzheimer Agents

Zou¹,

Qian²,

Liu³

et al. 2022

ChemistrySelect

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Twenty-four genistein-O-1,3,5-triazine derivatives were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. These compounds were confirmed by IR, NMR and HRMS and single-crystal X-ray diffraction studies. Most target compounds showed good inhibition and selectivity to acetylcholinesterase. Among these compounds, compound 4 e (7-((4-chloro-6-(diisobutylamino)-1,3,5-triazin-2-yl)oxy)-5hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) exhibited the strongest inhibition to acetylcholinesterase with IC 50 of 0.034 μM, which was comparable with that of donepezil (IC 50 = 0.037 μM). The enzyme kinetics studies showed that this compound was a kind of mixed type inhibitor. Molecular docking and molecular dynamics simulations study of this compound indicated that it could interact with the crucial amino acids present at the catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase and bind to acetylcholinesterase stably. Furthermore, this compound also showed terrific metal chelating abilities. ADMET characteristics implied that these compounds could possess the properties to become drug candidates. Thus, this compound may become a latent multifunctional anti-Alzheimer agent.

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Potential of triazines in Alzheimer's disease: A versatile privileged scaffold

Cited by 10 publications

References 69 publications

A Review of the Current Status of Disease-Modifying Therapies and Prevention of Alzheimer’s Disease

A Review of the Current Status of Disease-Modifying Therapies and Prevention of Alzheimer’s Disease

Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

Design, Synthesis, Biological Evaluation and Molecular Dynamics Simulations Study of Genistein‐O‐1,3,5‐Triazine Derivatives as Multifunctional Anti‐Alzheimer Agents

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