Fighting Against Alzheimer's Disease: Synthesis of New Pyrazoline and Benzothiazole Derivatives as New Acetylcholinesterase and MAO Inhibitors

Turan-Zitouni, Gülhan; Hussein, Weiam; Sağlık, Begüm Nurpelin; Baysal, Merve; Kaplancıklı, Zafer Asım

doi:10.2174/1570180814666170704144917

Cited by 7 publications

(6 citation statements)

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“…This property facilitated a systematic investigation [ 19 , 20 , 21 ]. When the literature studies are evaluated, it can be learned that benzazole derivatives have inhibitory activity on acetylcholinesterase enzyme [ 17 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. In addition, some benzimidazole derivatives have been shown to be useful as amyloid imaging probes because of their high binding affinity to Aβ aggregates and high uptake into the brain [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

et al. 2019

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Alzheimer’s disease (AD), one of the main causes of aged dementia, is a progressive and degenerative neurological disorder characterized by loss of cognition and memory. Although the symptomatic treatment of AD, particularly acetylcholinesterase inhibitors (AChEIs) based on the ‘cholinergic hypothesis’, has been successful in clinic, at present there is no cure for this disease. In this study, we designed compounds carrying benzimidazole and triazole rings on the same chemical skeleton so as to investigate their potential acetylcholinesterase and butyrylcholinesterase activity. Furthermore, molecular modeling study was performed to determine the binding mode of the best inhibitor to the AChE. Among them, compounds 3d and 3h, which featured 3,4-dihydroxy substitution at the phenyl ring and 5(6)-chloro substitution at the benzimidazole ring were found to be potent inhibitors of AChE. The inhibition kinetics of the two most active derivatives 3d and 3h were further studied. The kinetic displayed increasing slope and increasing intercept, which is consistent with a mixed inhibition. The IC50 and Ki values of 3d are 31.9 ± 0.1 nM and 26.2 nM, respectively. Compound 3h exhibited IC50 of 29.5 ± 1.2 nM and Ki of 24.8 nM. The above data compared favorably with data for donepezil (21.8 ± 0.9 nM) the reference compound in our study.

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Section: Introductionmentioning

confidence: 99%

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

et al. 2019

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“…Zitouni et al prepared 5 pyrazolines (Scheme ) and reported their anti-AChE activity. 1-[5-(Benzo[d][1,3]dioxol-5-yl)-3-(thien-2-yl)-4,5-dihydro-1 H -pyrazol-1-yl]-2-[(((4-(diethylamino)butyl)amino)methyl)thio]ethan-1-one ( A09 ) showed AChE inhibitory activity with an IC 50 value of 18.53 μM . A molecular docking studies was conducted against the most potent compound ( A08 ) in the series against VX-phosphonylated hAChE (PDB ID: 6U37) to assess the binding affinity.…”

Section: Pyrazolines As Ach Aβ and Tau Inhibitorsmentioning

confidence: 99%

Pyrazoline Containing Compounds as Therapeutic Targets for Neurodegenerative Disorders

Ahsan¹,

Ali

et al. 2022

ACS Omega

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Pyrazolines are a significant class of heterocyclic compounds with essential biological activities. They are quite stable, which has inspired medicinal chemists to experiment with the ring's structure in many different ways to create a variety of pharmacological activities. The structures of numerous commercially available therapeutic agents contain a pyrazoline ring. Pyrazolines are well-known for their ability to treat neurodegenerative diseases. The neurodegenerative diseases that affect huge populations globally include Alzheimer's disease (AD), Parkinson's disease (PD), and psychiatric disorders. The neuroprotective properties of pyrazolines published since 2003 are covered in the current review. Structure−activity relationships (SARs), molecular docking simulation, anticholinesterase (anti-AChE), and monoamine oxidase (MAO A/B) inhibitory actions are all covered in this article. Pyrazolines were discovered to have beneficial effects in the management of AD and were revealed to be inhibitors of acetylcholine esterase (AChE) and beta-amyloid (A β ) plaques. They were discovered to be efficient against PD and also targeted MAO B and COMT. It was discovered that the pyrazolines block MAO A to treat psychiatric diseases. Pyrazolines are significant heteroaromatic scaffolds with a variety of biological functions. They were discovered to be remarkably stable and serve as an indispensable anchor for the development of new drugs. By blocking AChE and MAOs, they may be used to treat neurodegenerative diseases. The discussion outlined here is an essential and helpful resource for medicinal chemists who are investigating and applying pyrazolines in neurodegenerative research initiatives as well as to expedite future research programs on neurodegenerative disorders.

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“…Different pyrazoline derivatives were synthesized and screened for their MAO inhibitory activities. Especially, substitution at 1, 3, and 5 positions of the pyrazoline nucleus displayed a significant activity towards MAO enzyme . There are also many thiazole compounds found to be effective against MAO enzymes in the literature …”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

Çevik

Osmaniye

Sağlık

et al. 2019

Journal of Heterocyclic Chem

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A novel series of 1,3,5‐trisubstituted‐2‐pyrazoline derivatives (4a‐4k) was synthesized and their chemical structures characterized by 1H NMR, 13C NMR, and mass spectroscopy. These compounds were evaluated as inhibitors for of type A and type B monoamine oxidase (MAO) enzymes. The most common inhibitors of MAO enzymes used to treat depression and anxiety such as selegiline and moclobemide drugs were used as reference agents. A result of biological evaluation of these compounds revealed compounds 4c, 4d, and 4ı as potent and selective MAO A inhibitors. The most active compound 4ı, which is 2,4‐dimethoxy at phenyl ring, showed strong inhibitory activity at MAO A (IC50 of 0.0445 ± 0.0018μM). Furthermore, compounds 4c and 4d showed significant inhibition profile on MAO A with the IC50 values 0.1423 ± 0.0051μM and 0.2148 ± 0.0067μM, respectively.

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Fighting Against Alzheimer's Disease: Synthesis of New Pyrazoline and Benzothiazole Derivatives as New Acetylcholinesterase and MAO Inhibitors

Cited by 7 publications

References 0 publications

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

Synthesis and AChE-Inhibitory Activity of New Benzimidazole Derivatives

Pyrazoline Containing Compounds as Therapeutic Targets for Neurodegenerative Disorders

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

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