Carbamate Derivatives Research Articles

Design, synthesis, and metabolite identification of Tamoxifen esterase-activatable prodrugs

Tamoxifen (TAM) is used in treatment of hormonal dependent breast cancer, both in premenopausal and postmenopausal women. TAM is intrinsically metabolized by CYP450 enzymes to more active metabolites. Recent reports identified CYP2D6, an enzyme involved in the conversion of TAM to the more potent 4-OH-TAM, is encoded by theCYP2D6gene, which is highly polymorphic. Women with inactive alleles are poor metabolizers; in many cases they suffer acquired TAM resistance. Herein we report synthesis and biological evaluation of novel TAM analogues. The novel analogues are designed to elude CYP2D6 metabolism. Hydrolysis of the carbamate moiety on ring C is mediated via carboxylesterases. Compound 3d [E/Z Benzyl-carbamic acid4-{2-benzyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-but-1-enyl}-phenyl ester] showed GI50 = 0.09 µM on MCF-7 and GI50 = 1.84 µM on MDA-MB231 cell lines. To further validate our hypothesis, metabolites of selected novel analogues were determined in vitro under different incubation conditions. The hydroxylated analogues were obtained under non CYP2D6 dependent conditions. Compound 8d, a benzyl carbamate derivative, was the least-stable analog and showed the highest rate of metabolism among all tested analogues. Our in silico model showed the novel flexible analogues can still adopt an antiestrogenic binding profile occupying the same pocket as 4-OH-TAM.

Immobilization of a cellulose carbamate-type chiral selector onto silica gel by alkyne-azide click chemistry for the preparation of chiral stationary chromatography phases

A new synthesis strategy for the preparation of cellulose derivative-based chiral selectors and the subsequent mild immobilization onto pre-functionalized silica gel are introduced, utilizing Cu(I)-catalyzed alkyne-azide Huisgen cycloaddition (“click”) chemistry. A cellulose 3,5-dimethylphenyl carbamate derivative carrying propynyl carbamate groups was prepared by a combination of carbonate aminolysis and isocyanate chemistry. For immobilization, 3-azidopropyl-functionalized silica gel as an inert carrier was used, synthesized via a 3-chloropropyl intermediate. The chiral selector, as well as the inorganic/organic hybrid materials (silica gel/chiral selector), were comprehensively characterized by ATR-FTIR, solid-state 13C and 29Si NMR, liquid-state NMR, GPC, TGA, and elemental analysis. The enantioseparation performance of the immobilized-type chiral stationary phase was evaluated by HPLC with a set of representative chiral test analytes and different eluents and compared to a respective coated-type (=non-covalently bound) chiral stationary phase carrying the same selector quality and quantity on the same silica gel matrix. The immobilization did not adversely affect the chiral separation performance; on the contrary, in some chromatographic separations the immobilized-type chiral stationary phase surprisingly even surpassed the coated reference material.Graphical abstract

Enantioselective Green HPLC Method for Simultaneous Determination of Enantiomer, and Potential Impurities in Apremilast Drug Substance

A single reversed-phase HPLC method was developed for the quantification of seven impurities of Apremilast and its enantiomer in the drug substance. An immobilized chiral stationary phase with a chiral selector “tris (3,5-dimethyl phenyl carbamate) derivative of amylose-Chiralpak IA-3 (250 mm × 4.6 mm, 3 μm) was employed to achieve the desired separation. A mobile phase consists of buffer (0.01M NH4HCO3, PH 8.0) and acetonitrile in the ratio 50:50 (v/v) and is pumped at a flow rate of 0.4 mL/min with an isocratic elution mode. The column oven temperature is set at 25°C, and the chromatographic output is monitored at 225 nm with a total run time of 45 min. A test concentration of 500 µg/mL of Apremilast in the mobile phase is used with an injection volume of 10 µL. Induced degradation studies were carried out to study the intrinsic chemical behavior of the drug. The degradation sample solutions were utilized to demonstrate the stability-indicating nature of the developed analytical method. The obtained mass number [M+H]+ for the primary degradation product formed in acid hydrolysis was identified as 418.36 and in base hydrolysis 478.12. The two impurities were identified as impurity-5(Deacetylated impurity), and impurity-2(open ring acid impurity), respectively, and the degradation pathways were established. Following ICH Q2 and USP<1225>guidelines, complete method validation was carried out. The RSD for the drug and impurities in interday and intraday studies are less than 4.0%, and the recoveries for the impurities are between 96.1-102.1% and linearity r ≥ 0.9997. LOQ results for the drug and impurities are between 0.052 µg/mL and 0.107 µg/mL, and LOD results are between 0.016 µg/mL and 0.032 µg/mL. The greenness of the method was evaluated by using an analytical eco scale, GAPI, and AGREE, and it was found that the method is green.

Reaction Mechanism of CO2 with Choline-Amino Acid Ionic Liquids: A Computational Study.

Carbon capture and sequestration are the major applied techniques for mitigating CO2 emission. The marked affinity of carbon dioxide to react with amino groups is well known, and the amine scrubbing process is the most widespread technology. Among various compounds and solutions containing amine groups, in biodegradability and biocompatibility perspectives, amino acid ionic liquids (AAILs) are a very promising class of materials having good CO2 absorption capacity. The reaction of amines with CO2 follows a multi-step mechanism where the initial pathway is the formation of the C-N bond between the NH2 group and CO2. The added product has a zwitterionic character and can rearrange to give a carbamic derivative. These steps of the mechanism have been investigated in the present study by quantum mechanical methods by considering three ILs where amino acid anions are coupled with choline cations. Glycinate, L-phenylalanilate and L-prolinate anions have been compared with the aim of examining if different local structural properties of the amine group can affect some fundamental steps of the CO2 absorption mechanism. All reaction pathways have been studied by DFT methods considering, first, isolated anions in a vacuum as well as in a liquid continuum environment. Subsequently, the role of specific interactions of the anion with a choline cation has been investigated, analyzing the mechanism of the amine-CO2 reaction, including different coupling anion-cation structures. The overall reaction is exothermic for the three anions in all models adopted; however, the presence of the solvent, described by a continuum medium as well as by models, including specific cation- -anion interactions, modifies the values of the reaction energies of each step. In particular, both reaction steps, the addition of CO2 to form the zwitterionic complex and its subsequent rearrangement, are affected by the presence of the solvent. The reaction enthalpies for the three systems are indeed found comparable in the models, including solvent effects.

Synthesis and characterization of carbamates derivatives from 4-amino-1,2,4-triazole

Carbamate derivatives are proved to be an essential class of molecules because of their application as drugs and prodrugs. Their several derivatives also have been used to craft the drug-target interfaces by incorporating the carbamate moiety. Due to the huge demand in pharma-industries these have been extensively explored and synthesized. The synthesis and characterization of carbamate derivatives from 4-amino-1,2,4-triazoles and 3-(methylthio)-4-amino-1,2,4-triazoles are described. Carbamate derivatives of 4-amino-1,2,4-triazoles with phenyl chloroformate in CH3CN using K2CO3 at ca. ~80°C have been synthesized with good to excellent yield (~81 to 97%). The methodology has been subsequently extended for synthesis of carbamate derivatives of 3-(methylthio)-4-amino-1,2,4-triazoles in which bicarbamate derivatives are formed as major products (~39 to 47%) along with mono carbamate derivatives as minor products (~9 to 22%) in the presence of similar solvent and base. On investigating the effect of solvent and base, the reaction in CH3CN in presence of K2CO3 shows the best results.

A safe alternative synthesis of primary carbamates from alcohols; in vitro and in silico assessments as an alternative acetylcholinesterase inhibitors

Carbamates are important molecules because they are used in various biochemical processes. In this study, effective alternative method for the synthesis of primary carbamates from alcohols was developed in the presence of chlorosulfonyl isocyanate (CSI) in pyridine at room temperature in mild conditions. The primary carbamates were synthesized excellent yield. This method is easy, practical, and inexpensive without any additive, metal, or catalyst. Alzheimer’s disease (AD) is a neurodegenerative disease and has been reported to affect approximately 50 million people worldwide in 2020. Drugs that reversibly inhibit the acetylcholinesterase (AChE) activity are used for the treatment of AD. For this reason, there is a growing interest in developing alternative AChE inhibitors. Concordantly, Anti-anticholinesterase activity of synthesized carbamate derivatives was investigated as an alternative AChE inhibitors. In order to determine the inhibitory effect of these molecules, IC50, and Ki values and inhibition types were determined. According to the Ki results, the most effective inhibitors were 3 b and 3e with the Ki values of 22 and 38 µM, respectively. It was found that all molecules showed competitive inhibition type. For clarify the inhibitors-enzyme interactions, molecular docking studies were performed and possible binding interactions between the synthesized molecules and AChE were determined. Additionally, the pharmacokinetic and properties of the synthesized molecules were evaluated in silico. Communicated by Ramaswamy H. Sarma.

A molecular docking-based comparative assessment of various anticholinergic drugs as antidotes to different nerve agent poisoning

Nerve agent poisoning is still a threat to civilization. Nerve agents function by binding with the enzyme acetylcholinesterase irreversibly. Accumulation of acetylcholine in the synapse causes over-stimulation of muscarinic and nicotinic acetylcholinergic receptors. Thus miosis, glandular hyper secretion, bronchoconstriction, vomiting, diarrhea and bradycardia occurs (by M1-M5 receptors stimulation); whereas convulsion and seizures occur due to the nicotinic receptors. Atropine is a non-selective muscarinic antagonists but no nicotinic antagonists are known. Seizures are controlled by diazepam. Enzyme aging occurs without treatment which causes the enzyme resistant to oxime therapy. Though numerous wet-lab based works has carried out, however, recent time there is an over-growing trend to make comparative assessment of drugs and toxicants. Here we made a molecular docking based comparative assessments between nerve agents toxicity and efficacy of different drugs to prevent this toxicity. Our results suggest that VX is the most harmful organophosphate nerve agents and HI-6 is the best drug followed by Obidoxime and Pralidoxime to free acetylcholinestarase. Docking results correspond the data trend of different in vivo experiments for the assessment of severity of different nerve agents and/or effectiveness of different antidote drugs. Our study reinforces the utility of pretreatment of the enzyme with a carbamic acid derivative like Pyridostigmine bromide which inhibits the enzyme reversibly to a smaller extent and thus, prevent the enzyme from aging and the nerve agent binding. Communicated by Ramaswamy H. Sarma

Synthesis and Evaluation of Novel (5S)-5-(Aminomethyl)-3-[4-(6,7-Dihydrothieno[3,2-c]Pyridin-5(4H)-yl)Phenyl]-1,3-Oxazolidin-2-One Derivatives as Potent Antimicrobial Agents

In the present work, a series of novel oxazolidinone derivatives containing thieno-pyridine ring system (11a–n) were synthesized in six steps. Synthesis of amino oxazolidinone scaffold (10) involved nucleophilic substitution of thienopyridine (4) with P-chloro-nitrobenzene (3) in dimethyl formamide at 65 °C give nitro compound (5) which was further reduced in catalytic hydrogenation condition using Raney-Nickel in isopropyl alcohol afforded amine (6). Reaction of compound (6) with 2-[(2S)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione (7) at mild reflux condition in isopropyl alcohol gives compound (8). Hydroxy amine compound (8) further undergo carbonyl insertion reaction with 1, 1’-carbonylbis(1H-imidazole) afforded oxazolidinone compound (9). The de-protection of phthalamide group of compound (9) carried by treating with aqueous solution of hydrazine hydrate in methanol at room temperature give compound (10). Finally, compound (10) reacts with acetyl chloride, carboxylic acid, sulfonyl chloride and chloro format by customary method provided amides, sulfonamide and carbamate derivative of (5S)-5-(aminomethyl)-3-[4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)phenyl]-1,3-oxazolidin-2-one. The developed synthetic approach was operationally simple and high yielding. The structures of the synthesized compounds were elucidated by IR, MS, 1H and 13C-NMR. Synthesized compounds (11a–n) were tested for antibacterial activity against a panel of Gram-positive bacteria comprising Staphylococcus aureus (ATCC5638), Streptococcus pyogenes (ATCC12344), Bacillus subtilis (ATCC6051), Bacillus pumilus (ATCC27142), and Enterococcus faecalis (NCIM5253). The investigation of antimicrobial screening data revealed that, most of the compounds tested have demonstrated sensible to good bacterial activity. In summary, preliminary results of activity indicate that, acetyl derivative (11a), methane sulfonamide derivative (11c) and p-toluene sulfonamide derivative (11e) found to be good activity and di-(methane sulfonamide) derivative (11d) showed comparable activity to reference drug substances.

Renewable Resources for Enantiodiscrimination: Chiral Solvating Agents for NMR Spectroscopy from Isomannide and Isosorbide.

A new family of chiral selectors was synthesized in a single synthetic step with yields up to 84% starting from isomannide and isosorbide. Mono- or disubstituted carbamate derivatives were obtained by reacting the isohexides with electron-donating arylisocyanate (3,5-dimethylphenyl- or 3,5-dimethoxyphenyl-) and electron-withdrawing arylisocyanate (3,5-bis(trifluoromethyl)phenyl-) groups to test opposite electronic effects on enantiodifferentiation. Deeper chiral pockets and derivatives with more acidic protons were obtained by derivatization with 1-naphthylisocyanate and p-toluenesulfonylisocyanate, respectively. All compounds were tested as chiral solvating agents (CSAs) in 1H NMR experiments with rac-N-3,5-dinitrobenzoylphenylglycine methyl ester in order to determine the influence of different structural features on the enantiodiscrimination capabilities. Some selected compounds were tested with other racemic analytes, still leading to enantiodiscrimination. The enantiodiscrimination conditions were then optimized for the best CSA/analyte couple. Finally, a 2D- and 1D-NMR study was performed employing the best performing CSA with the two enantiomers of the selected analyte, aiming to determine the enantiodiscrimination mechanism, the stoichiometry of interaction, and the complexation constant.

QSTR Modeling to Find Relevant DFT Descriptors Related to the Toxicity of Carbamates.

Compounds containing carbamate moieties and their derivatives can generate serious public health threats and environmental problems due their high potential toxicity. In this study, a quantitative structure–toxicity relationship (QSTR) model has been developed by using one hundred seventy-eight carbamate derivatives whose toxicities in rats (oral administration) have been evaluated. The QSRT model was rigorously validated by using either tested or untested compounds falling within the applicability domain of the model. A structure-based evaluation by docking from a series of carbamates with acetylcholinesterase (AChE) was carried out. The toxicity of carbamates was predicted using physicochemical, structural, and quantum molecular descriptors employing a DFT approach. A statistical treatment was developed; the QSRT model showed a determination coefficient (R2) and a leave-one-out coefficient (Q2LOO) of 0.6584 and 0.6289, respectively.

Synthesis and evaluation of carbamate derivatives as fatty acid amide hydrolase and monoacylglycerol lipase inhibitors.

Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are the primary catabolic enzymes for endocannabinoids, anandamide (AEA), and 2-arachidonoyl glycerol. Numerous studies have shown that FAAH and MAGL play an important role in modulating various central nervous system activities; hence, the development of small molecule FAAH/MAGL inhibitors is an active area of research. Several small molecules possessing the carbamate scaffold are documented as potential FAAH/MAGL inhibitors. Here, we designed and synthesized a series of open chain and cyclic carbamates and evaluated their dual FAAH-MAGL inhibition properties. Phenyl [4-(piperidin-1-ylmethyl)phenyl]carbamate (2e) emerged as the most potent MAGL inhibitor (IC50 = 19 nM), benzyl (1H-benzo[d]imidazol-2-yl)carbamate (3h) was the most potent FAAH inhibitor (IC50 = 55 nM), and phenyl (6-fluorobenzo[d]thiazol-2-yl)carbamate (2i) egressed as a nonselective dual FAAH-MAGL inhibitor (FAAH: 82 nM, MAGL: 72 nM). The enzyme kinetics experiments revealed that the compounds inhibit FAAH/MAGL in a covalent-reversible manner, with a mixed binding mode of action. Moreover, the lead compounds were found suitable for blood-brain permeation in the parallel artificial membrane permeation assay. Furthermore, docking simulation experiments suggested that the potency of the lead compounds was governed by hydrogen bonds and hydrophobic interactions with the enzyme active sites. In silico drug-likeness and ADMETox prediction studies provided useful information on the compounds' oral absorption, metabolism, and toxicity profiles. In summary, this study afforded potent multifunctional carbamates with appreciable pharmacokinetic profiles meriting further investigation.

Divergent Synthesis of 2-Cyanoaryl Carbamate and 2-Cyanoaryl Urea Derivatives via Hypervalent Iodine-Induced C-C Bond Cleavage.

Divergent synthetic methods for transforming isatins to 2-cyanoaryl carbamate and 2-cyanoaryl urea derivatives were developed using ammonium carbamate as the nitrogen source and iodobenzene diacetate as the oxidant. This reaction features mild conditions, broad substrate scope, and moreover, the use of toxic cyano-containing compounds is avoided.

Design, synthesis, biologically evaluation and molecular docking of C-glycosidic oximino carbamates as novel OfHex1 inhibitors

The inhibition of function-specific β-N-acetyl-D–hexosaminidases, such as OfHex1 from the Asian corn borer (Ostrinia furnacalis), is a promising strategy for the development of green pesticides. Among reported OfHex1 inhibitors, glycosyl inhibitors show especially high inhibitory activity. In this study, a series of novel C-glycosidic oximino carbamate derivatives were designed using the OfHex1 crystal structure and synthesized. Among the C-Glycoside derivatives studied, compound 7k exhibited the best inhibitory activity against OfHex1 (IC50 = 47.47 μM). Compound 7k also exhibited excellent larvicidal activity against Plutella xylostella. The potential inhibitory mechanism of 7k was studied using molecular docking. Notably, compound 7k is the first reported C-glycoside inhibitor of OfHex1. These results provide direction for the rational design of novel OfHex1 inhibitors.

Unravelling the Supramolecular Driving Forces in the Formation of CO2-Responsive Pseudopeptidic Low-Molecular-Weight Hydrogelators.

A new family of C2-symmetric pseudopeptides with a high functional density for supramolecular interactions has been synthetized through the attachment of four amino acid subunits to a diamino aliphatic spacer. The resulting open-chain compounds present remarkable properties as low-molecular-weight hydrogelators. The self-assembled 3D networks were characterized by SEM analyses, observing regular nanofibres with 80–100 nm diameters. Spectroscopic and molecular modelling experiments revealed the presence of strong synergic effects between the H-bonding and π–π interactions, with the best results obtained for the homoleptic tetra-pseudopeptide derived from l-Phe. In addition, these bioinspired hydrogels possessed pH- and CO2-responsive sol–gel transitions. The formation of ammonium carbamate derivatives in the presence of carbon dioxide led to a detrimental change in its adequate self-assembly. CO2 desorption temperatures of ca. 70 °C were assigned to the thermodynamically favoured recovery of the supramolecular gel.

Design, Synthesis and Biological Activity of New Carbamate Cholinesterase Inhibitors

The work deals with the design, synthesis and biological activity of new carbamate cholinesterase inhibitors. It is focused on selected syntheses of new carbamate derivatives, which were tested for their anticholinesterase activity against acetylcholinesterase as well as butyrylcholinesterase. Despite various theories in the pathogenesis of Alzheimer's disease, drugs that can inhibit these two enzymes still represent the major approach to the treatment of this neurodegenerative disease. Many of the newly synthesized compounds have unique chemical structure. Recently, the approach to the synthesis of new cholinesterase inhibitors has focused on the preparation of potential drugs, containing in their chemical structure fragments of already known drugs, commonly used in the pharmacotherapy of Alzheimer's disease, but also other diseases. The aim of preparing these compounds is to affect several biological systems simultaneously. These multipotent compounds have been termed "multi-target-directed ligands"; the molecules of drugs used to treat Alzheimer's disease always contain a pharmacophore acting as a cholinesterase inhibitor, which represents the mainstay of therapy.

Anti-Proliferative and Cytoprotective Activity of Aryl Carbamate and Aryl Urea Derivatives with Alkyl Groups and Chlorine as Substituents.

Natural cytokinines are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of aryl carbamate, pyridyl urea, and aryl urea cytokinine analogs with alkyl and chlorine substitutions and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Aryl carbamates with the oxamate moiety were selectively anti-proliferative for the cancer cell lines tested, while the aryl ureas were inactive. In the cytoprotection studies, the same aryl carbamates were able to counteract the CoCl2 cytotoxicity by 3–8%. The possible molecular targets of the aryl carbamates during the anti-proliferative action were the adenosine A2 receptor and CDK2. The obtained results are promising for the development of novel anti-cancer therapeutics.

Quantitative Retention (Structure)-Activity Relationships in Predicting the Pharmaceutical and Toxic Properties of Potential Pesticides.

The micellar liquid chromatography technique and quantitative retention (structure)–activity relationships method were used to predict properties of carbamic and phenoxyacetic acids derivatives, newly synthesized in our laboratory and considered as potential pesticides. Important properties of the test substances characterizing their potential significance as pesticides as well as threats to humans were considered: the volume of distribution, the unbonded fractions, the blood–brain distribution, the rate of skin and cell permeation, the dermal absorption, the binding to human serum albumin, partitioning between water and plants’ cuticles, and the lethal dose. Pharmacokinetic and toxicity parameters were predicted as functions of the solutes’ lipophilicities and the number of hydrogen bond donors, the number of hydrogen bond acceptors, and the number of rotatable bonds. The equations that were derived were evaluated statistically and cross-validated. Important features of the molecular structure influencing the properties of the tested substances were indicated. The QSAR models that were developed had high predictive ability and high reliability in modeling the properties of the molecules that were tested. The investigations highlighted the applicability of combined chromatographic technique and QS(R)ARs in modeling the important properties of potential pesticides and reducing unethical animal testing.

Hybrid imidazo[1,2-a]pyridine analogs as potent ATX inhibitors with concrete in vivo antifibrosis effect.

In recent years, small-molecule inhibitors targeting the autotaxin (ATX)/lysophosphatidic acid axis gradually brought excellent disease management benefits. Herein, a series of imidazo[1,2-a]pyridine compounds (1-11) were designed as ATX inhibitors through a hybrid strategy by combining the imidazo[1,2-a]pyridine skeleton in GLPG1690 and the benzyl carbamate moiety in PF-8380. As indicated by FS-3-based enzymatic assay, the carbamate derivatives revealed moderate to satisfying ATX inhibitory potency (IC50 = 23-343 nM). Subsequently, the carbamate linker was altered to a urea moiety (12-19) with the aim of retaining ATX inhibition and improving the druglikeness profile. The binding mode analysis all over the modification process well rationalized the leading activity of urea derivatives in an enzymatic assay. Following further structural optimization, the diethanolamine derivative 19 exerted an amazing inhibitory activity (IC50 = 3.98 nM) similar to the positive control GLPG1690 (IC50 = 3.72 nM) and PF-8380 (IC50 = 4.23 nM). Accordingly, 19 was tested directly for in vivo antifibrotic effects through a bleomycin model (H&E staining), in which 19 effectively alleviated lung structural damage and fibrosis at an oral dose of 20 and 60 mg/kg. Collectively, 19qualified as a promising ATX inhibitor for potential application in fibrosis-relevant disease treatment.

Design, Synthesis, and In Vitro, In Silico and In Cellulo Evaluation of New Pyrimidine and Pyridine Amide and Carbamate Derivatives as Multi-Functional Cholinesterase Inhibitors

Alzheimer disease is an age-linked neurodegenerative disorder representing one of the greatest medical care challenges of our century. Several drugs are useful in ameliorating the symptoms, even if none could stop or reverse disease progression. The standard approach is represented by the cholinesterase inhibitors (ChEIs) that restore the levels of acetylcholine (ACh) by inhibiting the acetylcholinesterase (AChE). Still, their limited efficacy has prompted researchers to develop new ChEIs that could also reduce the oxidative stress by exhibiting antioxidant properties and by chelating the main metals involved in the disease. Recently, we developed some derivatives constituted by a 2-amino-pyrimidine or a 2-amino-pyridine moiety connected to various aromatic groups by a flexible amino-alkyl linker as new dual inhibitors of AChE and butyrylcholinesterase (BChE). Following our previous studies, in this work we explored the role of the flexible linker by replacing the amino group with an amide or a carbamic group. The most potent compounds showed higher selectivity against BChE in respect to AChE, proving also to possess a weak anti-aggregating activity toward Aβ42 and tau and to be able to chelate Cu2+ and Fe3+ ions. Molecular docking and molecular dynamic studies proposed possible binding modes with the enzymes. It is noteworthy that these compounds were predicted as BBB-permeable and showed low cytotoxicity on the human brain cell line.

Research of new acetylcholinesterase inhibitors based on QSAR and molecular docking studies of benzene-based carbamate derivatives

Research of new acetylcholinesterase inhibitors based on QSAR and molecular docking studies of benzene-based carbamate derivatives