71009-17-1Relevant academic research and scientific papers
Azole antifungal compounds could have dual cholinesterase inhibitory potential according to virtual screening, enzyme kinetics, and toxicity studies of an inhouse library
Barut, Burak,Sari, Suat,Sabuncuo?lu, Suna,?zel, Arzu
, (2021/03/23)
Recent advances in cholinesterase inhibitors opened new venues for the treatment of cognitive disorders like Alzheimer's disease. Certain azole antifungals like miconazole were reported to have cholinesterase inhibitory effects and hence ameliorate cognitive deficits. In this study, we tested a set of azole antifungal derivatives selected through virtual screening of an inhouse library for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects. Compound 61 showed potent and selective AChE inhibition (IC50 = 8.77 μM). The study also yielded dual AChE/BChE inhibitors in addition to a number of potent AChE inhibitors. Enzyme kinetics assays revealed that AChE inhibitors were competitive inhibitors. All the active compounds were imidazole derivatives and the modeling study showed that imidazole at protonated state contributed greatly to the binding interactions with some key residues of AChE and BChE active site. The active derivatives had negligible cytotoxic effects on murine fibroblast viability. According to our results, compounds featuring the classical scaffold of azole antifungal drugs could hold high potential for anticholinesterase drug design.
Diaryl-containing imidazole compound and preparation method and medical application thereof
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Paragraph 0201; 0206; 0207, (2019/02/21)
The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
Synthesis, in vivo anticonvulsant testing, and molecular modeling studies of new nafimidone derivatives
Acar, Mustafa F.,Sari, Suat,Dalkara, Sevim
, p. 606 - 616 (2019/04/26)
An estimated 50 million people suffer epilepsy worldwide and 30% of the cases do not respond to current antiepileptic drugs (AEDs). Here, we report synthesis and anticonvulsant screening of new derivatives of nafimidone, a well-known member of (arylakyl)azole anticonvulsants. The compounds showed promising protection against maximal electroshock (MES)-induced seizures in mice and rats when administered via intraperitoneal (ip) and oral route. Especially, 5b, 5c, and 5i displayed outstanding activity in rats in MES test when given ip (ED50: 16.0, 15.8, and 11.8 mg/kg, respectively). Additionally, 5l was active against 6 Hz and corneal-kindled mice models. Behavioral toxicity of the compounds was very low and their therapeutic indexes were high compared to some currently available AEDs. A number of pharmaceutically relevant descriptors and properties were predicted for the compounds in silico in comparison with a set of known drugs. Favorable results were obtained such as good blood–brain barrier permeability and high oral absorption, as well as drug-likeness. 5l was found to show affinity to the benzodiazepine binding site of A-type GABA receptor via molecular docking simulations.
Synthesis, anticonvulsant and antimicrobial activities of some new 2-acetylnaphthalene derivatives
Karakurt, Arzu,?zalp, Meral,I?ik, ?amil,Stables, James P.,Dalkara, Sevim
scheme or table, p. 2902 - 2911 (2010/07/04)
In this study, as a continuation of our research for new (arylalkyl)imidazole anticonvulsant compounds, the design, synthesis and anticonvulsant/antimicrobial activity evaluation of a series of 2-acetylnaphthalene derivatives have been described. Molecular design of the compounds has been based on the modification of nafimidone [1-(2-naphthyl)-2-(imidazol-1-yl)ethanone], which is a representative of the (arylalkyl)imidazole anticonvulsant compounds as well as its active metabolite, nafimidone alcohol (3, 4). In general, these compounds were variously substituted at the alkyl chain between naphthalene and imidazole rings and subjected to some other modifications to evaluate additional structure-activity relationships. The anticonvulsant activity profile of those compounds was determined by maximal electroshock seizure (MES) and subcutaneous metrazol (scM) seizure tests, whereas their neurotoxicity was examined using rotarod test. All the ester derivatives of nafimidone alcohol (5a-h), which were designed as prodrugs, showed anticonvulsant activity against MES-induced seizure model. Four of the most active compounds were chosen for further anticonvulsant evaluations. Quantification of anticonvulsant protection was calculated via the ip route (ED50 and TD50) for the most active candidate (5d). Observed protection in the MES model was 38.46 mg kg-1 and 123.83 mg kg-1 in mice and 20.44 mg kg-1, 56.36 mg kg-1 in rats, respectively. Most of the compounds with imidazole ring also showed antibacterial and/or antifungal activities to a certain extent in addition to their anticonvulsant activity.
Aromatic ethers of 1-aryl 2-(1H-azolyl)ethanol: study of antifungal activity
Wahbi, Y.,Caujolle, R.,Tournaire, C.,Payard, M.,Linas, M. D.,Seguela, J. P.
, p. 955 - 962 (2007/10/03)
Aromatic ethers related to antifungal azole miconazole were synthesized and tested against various strains of Candida.We found that activity is related to the nature of the aromatic ring and the position of substituents on this ring.Activity is more strongly dependent on the substituent in the 2-position of the ethyl chain on the aromatic group linked through the oxygen.Triazoles were always less potent than the corresponding imidazole analogues. - Keywords: imidazole; 1,2,4-triazole; antifungal activity; yeast; structure-activity relationship
1-(Naphthylalkyl)-1H-imidazole derivatives, a new class of anticonvulsant agents
Walker,Wallach,Hirschfeld
, p. 67 - 74 (2007/10/02)
Potent anticonvulsant activity has been demonstrated for a large number of 1-(naphthylalkyl)-1H-imidazoles containing a variety of functional groups in the alkylene bridge. The presence of a small oxygen function in the bridge, in general, confers a high
Imidazole derivatives, their preparation and their use in pharmaceutical compositions
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, (2008/06/13)
Imidazole derivatives of the formula , wherein R is alkyl, benzyl, substituted benzyl, phenyl or substituted phenyl, said substituted benzyl and substituted phenyl substituted on the phenyl ring with from one to three substituents independently selected from the group consisting of halo, lower alkyl and trifluoromethyl; X is oxygen or sulfur; and the pharmaceutically acceptable acid addition salts thereof are CNS-active agents, inhibitors of gastric secretion and antifugal, antibacterial and antiprotozoal agents. Processes are described for their preparation from the corresponding compounds , , , or , when Z is a conventional leaving group.
N-(naphthylethyl)imidazole derivatives
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, (2008/06/13)
Compounds of the formula STR1 wherein R is alkyl, benzyl, substituted benzyl, phenyl or substituted phenyl, said substituted benzyl and substituted phenyl substituted on the phenyl ring with from one to three substituents independently selected from the g
1-(Naphthylethyl)imidazole derivatives
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, (2008/06/13)
Compounds of the formula STR1 wherein Z is hydroxymethylene, esterified hydroxymethylene, carbonyl, or ketal-, thioketal- or hemithioketal- protected carbonyl, and the pharmaceutically acceptable acid addition salts thereof, are useful as anticonvulsant a
