Synthesis and Evaluation of A New Series of Thiazolyl-Pyrazoline Derivatives as Cholinesterase Inhibitors

Temel, Halide Edip; Altıntop, Mehlika Dilek; Özdemır, Ahmet

doi:10.4274/tjps.20982

Cited by 11 publications

(17 citation statements)

References 34 publications

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“…[32][33][34][35][36][37][38][39][40][41] In a previous work conducted by our research team, [39] 1-(4-phenylthiazol- were identified as promising dual hCA/AChE inhibitors exerting their action at nanomolar levels (Figure 2). In the next process of our ongoing research on dual hCA/AChE inhibitors designed based on the molecular hybridization of thiazole and pyrazoline scaffolds, [15,39,42] herein, new thiazolyl-pyrazolines (4a-k) were synthesized according to a facile and versatile synthetic route. These compounds were subjected to in vitro and in silico studies to determine their potencies as hCA I, hCA II, and AChE inhibitors.…”

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confidence: 99%

Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds

Sever

Türkeş

Altıntop

et al. 2021

Archiv der Pharmazie

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New hybrid thiazolyl-pyrazoline derivatives (4a-k) were obtained through a facile and versatile synthetic procedure, and their inhibitory effects on the human carbonic anhydrase (hCA) isoforms I and II as well as on acetylcholinesterase (AChE) were determined.All new thiazolyl-pyrazolines showed activity at nanomolar levels as hCA I, hCA II, and AChE inhibitors, with K I values in the range of 13.35-63.79, 7.01-115.80, and 17.89-48.05 were identified as highly potent inhibitors, superior to the standard drugs, acetazolamide and tacrine, respectively. Compounds 4a-k were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. Moreover, a comprehensive ligand-receptor interaction prediction was performed using the ADME-Tox, Glide XP, and MM-GBSA modules of the Schrödinger Small-Molecule Drug Discovery Suite to elucidate the potential binding modes of the new hybrid inhibitors against these metabolic enzymes.

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confidence: 99%

Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds

Sever

Türkeş

Altıntop

et al. 2021

Archiv der Pharmazie

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“…As a part of this study, the compliance of the compounds to Lipinski's RO5 was evaluated. Naphthalene-substituted compound 99 was the most potent AChE inhibitor (IC 50 = 38.5 µg mL −1 ), whereas fluoro-substituted compound 100 was the most effective BChE inhibitor (IC 50 = 43.02 µg mL −1 ) in this series relative to the standard galantamine (IC 50 = 97.17 µg mL −1 for AChE; 80.98 µg mL −1 for BChE) 200 ( Table 4 ).…”

Section: Synthetic Cholinesterase Inhibitorsmentioning

confidence: 93%

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

et al. 2022

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“…Temel et al synthesized thiazolyl-pyrazoline derivatives via a ring closure reaction of 3-(2-furyl)-5-(1,3-benzodioxol-5-yl)-1-thiocarbamoyl-4,5-dihydro-1 H -pyrazole with 2-bromo-1-arylethanones (Scheme ). 2-[5-(1,3-Benzodioxol-5-yl)-3-(2-furyl)-4,5-dihydro-1 H -pyrazol-1-yl]-4-(naphthalen-2-yl)thiazole ( A16 ) was found to be the most effective AChE inhibitor (38.5 ± 2.85%), at 80 μg/mL . A molecular docking study was conducted against the most potent compound ( A16 ) 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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Synthesis and Evaluation of A New Series of Thiazolyl-Pyrazoline Derivatives as Cholinesterase Inhibitors

Cited by 11 publications

References 34 publications

Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds

Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

Pyrazoline Containing Compounds as Therapeutic Targets for Neurodegenerative Disorders

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