Design, synthesis, in vitro and in vivo evaluation of novel pyrrolizine-based compounds with potential activity as cholinesterase inhibitors and anti-Alzheimer's agents

El‐Sayed, Nehad A.; Farag, Awatef El-Said; Ezzat, Manal Abdel Fattah; Akıncıoğlu, Hülya; Gülçın, İlhami; Abou‐Seri, Sahar M.

doi:10.1016/j.bioorg.2019.103312

Cited by 33 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The final volume was completed to 100 µL and changes in the absorption were followed at 412 nm. The IC50 values of the compounds were calculated via activity (%) versus compounds concentration plots [33].…”

Section: Acetylcholinesterase Inhibitory Assaymentioning

confidence: 99%

Acetylcholinesterase inhibitory potencies of new pyrazoline derivatives

Tuğrak¹,

Gül²,

Gülçin³

2020

jrp

View full text Add to dashboard Cite

Alzheimer's disease (AD) has no current cure and its mechanism is not fully known, but treatments for symptoms are available. Acetylcholinesterase (AChE) has been reported to be an applicable therapeutic target in patient with AD. Acetylcholinesterase inhibitors (AChEIs) are commonly used for it. For this purpose, novel series of pyrazoline based compounds [2-(3-(4-methoxyphenyl)-5-aryl-4,5-dihydro-1H-pyrazol-1-yl)benzo[d]thiazole, 1-9] were synthesized and AChE inhibitory potencies were reported here. The results indicated that compound 1 (Ki= 0.13±0.004 μM) possessed the highest AChE inhibitory effect in series, which is two times more potent than the reference compound Tacrin (Ki= 0.26±0.045 μM). So, pyrazoline derivative 1 can be considered as a lead inhibitor in designing new AChE inhibitors.

show abstract

Section: Acetylcholinesterase Inhibitory Assaymentioning

confidence: 99%

Acetylcholinesterase inhibitory potencies of new pyrazoline derivatives

Tuğrak¹,

Gül²,

Gülçin³

2020

jrp

View full text Add to dashboard Cite

show abstract

“…Alzheimer's disease (AD) is the most common form of dementia in elderly people, which generally occurs due to the progressive dysfunction of cholinergic neurons as a result of the β‐amyloid accumulation in some selected portions of the hippocampus and the cortex, which results in a decrease of learning and memory. [ 17–19 ] Until date, there are several molecular factors and mechanisms have been claimed that the role of acetylcholine (ACh) in amyloid β‐protein (Aβ‐protein), N ‐methyl‐ d ‐aspartate receptor, tau neurofibrillary tangles, and oxidative stress, dyshomeostasis of biometals are recorded. [ 19,20 ] Also, several hypotheses based on these factors have been proposed to explain the mechanism of AD development.…”

Section: Introductionmentioning

confidence: 99%

“…[ 17–19 ] Until date, there are several molecular factors and mechanisms have been claimed that the role of acetylcholine (ACh) in amyloid β‐protein (Aβ‐protein), N ‐methyl‐ d ‐aspartate receptor, tau neurofibrillary tangles, and oxidative stress, dyshomeostasis of biometals are recorded. [ 19,20 ] Also, several hypotheses based on these factors have been proposed to explain the mechanism of AD development. The role of ACh deficit is well known to be associated with the AD.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3‐triazole‐acetamide hybrid derivatives

Sepehri

Mohammadi‐Khanaposhtani

Asemanipoor

et al. 2020

Archiv der Pharmazie

View full text Add to dashboard Cite

Coumarins and their derivatives are receiving increasing attention due to numerous biochemical and pharmacological applications. In this study, a series of novel coumarin-1,2,3-triazole-acetamide hybrids was tested against some metabolic enzymes including α-glycosidase (α-Gly), α-amylase (α-Amy), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), human carbonic anhydrase I (hCA I), and hCA II. The new coumarin-1,2,3-triazole-acetamide hybrids showed K i values in the

show abstract

“…Modern AD therapy targets enhance cholinergic neurotransmission by way of AChE inhibitors (AChEIs). Widely used AChEIs are galantamine, donepezil, and rivastigmine [4,5]. However, these drugs are unfortunately less effective to block AD progression, and they also have side effects [6].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and bioactivities of 1-(4-hydroxyphenyl)-2-((heteroaryl)thio)ethanones as carbonic anhydrase I, II and acetylcholinesterase inhibitors

et al. 2020

View full text Add to dashboard Cite

The discovery of enzyme targeting inhibitors is a popular area of drug research. Biological activities of the compounds bearing phenol and heteroaryl groups make them popular groups in drug design targeting important enzymes such as acetylcholinesterase (AChE, E.C.3.1.1.7) and carbonic anhydrases (CAs, EC 4.2.1.1). 1-(4-hydroxyphenyl)- 2-((aryl)thio)ethanones as possible AChE and CAs inhibitors were synthesized, and their chemical structures were confirmed by IR, 1 H NMR, 13 C NMR, and HRMS. The compounds 2 and 4 were found potent AChE inhibitors with the Ki values of 22.13 ±1.96 nM and 23.71 ±2.95 nM, respectively, while the compounds 2 (Ki = 8.61 ±0.90 nM, on hCA I) and 1 (Ki = 8.76 ±0.84 nM, on hCA II) had considerable CAs inhibitory potency. The lead compounds may help the scientists for the rational designing of an innovative class of drug candidates targeting enzyme-based diseases.

show abstract

Design, synthesis, in vitro and in vivo evaluation of novel pyrrolizine-based compounds with potential activity as cholinesterase inhibitors and anti-Alzheimer's agents

Cited by 33 publications

References 30 publications

Acetylcholinesterase inhibitory potencies of new pyrazoline derivatives

Acetylcholinesterase inhibitory potencies of new pyrazoline derivatives

Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3‐triazole‐acetamide hybrid derivatives

Synthesis and bioactivities of 1-(4-hydroxyphenyl)-2-((heteroaryl)thio)ethanones as carbonic anhydrase I, II and acetylcholinesterase inhibitors

Contact Info

Product

Resources

About