71009-17-1Relevant articles and documents
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.
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.
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
