5818-06-4Relevant articles and documents
Novel arylcarbamate-N-acylhydrazones derivatives as promising BuChE inhibitors: Design, synthesis, molecular modeling and biological evaluation
Yamazaki, Diego A.S.,Rozada, Andrew M.F.,Baréa, Paula,Reis, Elaine C.,Basso, Ernani A.,Sarragiotto, Maria Helena,Seixas, Flávio A.V.,Gauze, Gisele F.
, (2021/01/18)
A novel series of arylcarbamate-N-acylhydrazones derivatives have been designed and synthesized as potential anti-cholinesterase agents. In vitro studies revealed that these compounds demonstrated selective for butyrylcholinesterase (BuChE) with potent inhibitory activity. The compounds 10a-d, 12b and 12d were the most potent BuChE inhibitors with IC50 values of 0.07–2.07 μM, highlighting the compound 10c (IC50 = 0.07 μM) which showed inhibitory activity 50 times greater than the reference drug donepezil (IC50 = 3.54 μM). The activity data indicates that the position of the carbamate group in the aromatic ring has a greater influence on the inhibitory activity of the derivatives. The enzyme kinetics studies indicate that the compound 10c has a non-competitive inhibition against BuChE with Ki value of 0.097 mM. Molecular modeling studies corroborated the in vitro inhibitory mode of interaction and show that compound 10c is stabilized into hBuChE by strong hydrogen bond interaction with Tyr128, π-π stacking interaction with Trp82 and CH?O interactions with His438, Gly121 and Glu197. Based on these data, compound 10c was identified as low-cost promising candidate for a drug prototype for AD treatment.
Preclinical evaluation of 1,2,4-triazole-based compounds targeting voltage-gated sodium channels (VGSCs) as promising anticonvulsant drug candidates
Kaproń, Barbara,?uszczki, Jarogniew J.,Siwek, Agata,Karcz, Tadeusz,Nowak, Gabriel,Zagaja, Miros?aw,Andres-Mach, Marta,Stasi?owicz, Anna,Cielecka-Piontek, Judyta,Kocki, Janusz,Plech, Tomasz
, (2019/11/13)
Epilepsy is a chronic neurological disorder affecting nearly 65–70 million people worldwide. Despite the observed advances in the development of new antiepileptic drugs (AEDs), still about 30–40% of patients cannot achieve a satisfactory seizure control. In our current research, we aimed at using the combined results of radioligand binding experiments, PAMPA-BBB assay and animal experimentations in order to design a group of compounds that exhibit broad spectrum of anticonvulsant activity. The synthesized 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivatives were primarily screened in the maximal electroshock-induced seizure (MES) test in mice. Next, the most promising compounds (17, 22) were investigated in 6 Hz (32 mA) psychomotor seizure model. Protective effect of compound 22 was almost similar to that of levetiracetam. Moreover, these compounds did not induce genotoxic and hemolytic changes in human cells as well as they were characterized by low cellular toxicity. Taking into account the structural requirements for good anticonvulsant activity of 4-alkyl-5-aryl-1,2,4-triazole-3-thiones, it is visible that small electron-withdrawing substituents attached to phenyl ring have beneficial effects both on affinity towards VGSCs and protective activity in the animal models of epilepsy.
Efficient Synthesis of 1,4-Bis(5-aryl-1,3,4-oxadiazol-2-yl)-2,3,5,6-tetrafluorobenzenes
Dhotre, B. K.,Khandebharad, A. U.,Pathan, A.,Raut, S. V.
, p. 1324 - 1326 (2020/10/02)
Abstract: An efficient acid-catalyzed condensation between substituted benzohydrazides and 2,3,5,6-tetrafluoroterephthalic acid to form 1,4-bis(5-aryl-1,3,4-oxadiazol-2-yl)-2,3,5,6-tetrafluorobenzenes is reported. The products were isolated in 74–87% yield and were characterized by 1H NMR, IR, and mass spectra.
