Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts

Padrtova, Tereza; Marvanova, Pavlina; Odehnalová, Klára; Kubínová, Renata; Parravicini, Oscar; Garro, Adriana; Enriz, Ricardo D.; Humpa, Otakar; Oravec, Michal; Mokrý, Petr

doi:10.3390/molecules22122048

Cited by 11 publications

(12 citation statements)

References 39 publications

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“…Introducing new functional groups, such as ester groups, and grafting other chain segments on the functional groups as needed produces novel structures, which will improve the stability or performance of QASs. Padrtova et al used p -aminobenzoic acid as a raw material to synthesize quaternary ammonium salts with acetylcholinease inhibitory activity . Padnya et al synthesized two configurations of QASs, p - tert -butylthiacalix[4]arene in cone (cone-R) and 1,3-alternate conformations (1,3- alt -R).…”

Section: Chemical Diversity Of Antibacterial Qassmentioning

confidence: 99%

Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications

Zhou

Zhou²,

Zhang

et al. 2023

Bioconjugate Chem.

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The overuse of antibiotics has led to the emergence of a large number of antibiotic-resistant genes in bacteria, and increasing evidence indicates that a fungicide with an antibacterial mechanism different from that of antibiotics is needed. Quaternary ammonium salts (QASs) are a biparental substance with good antibacterial properties that kills bacteria through simple electrostatic adsorption and insertion into cell membranes/altering of cell membrane permeability. Therefore, the probability of bacteria developing drug resistance is greatly reduced. In this review, we focus on the synthesis and application of single-chain QASs, double-chain QASs, heterocyclic QASs, and gemini QASs (GQASs). Some possible structure–function relationships of QASs are also summarized. As such, we hope this review will provide insight for researchers to explore more applications of QASs in the field of antimicrobials with the aim of developing systems for clinical applications.

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Section: Chemical Diversity Of Antibacterial Qassmentioning

confidence: 99%

Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications

Zhou

Zhou²,

Zhang

et al. 2023

Bioconjugate Chem.

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“…We have proved that QTAIM calculations are a useful tool in the study of enzyme-ligand complexes with different structural complexity, since they provide accurate information of molecular interactions that take part in complexes formation [62]. In addition, we have recently applied this technique to the study of different complexes of both AChE and BChE [66,67]. Based on those results, we carried out a QTAIM study for compounds 5c and 5k, both with high inhibitory effect against BChE.…”

Section: Qtaim Calculationsmentioning

confidence: 99%

“…This methodology was successfully applied in previous works [60][61][62][63][64][65]. Indeed, we have formerly reported and described the molecular interactions established in the active site of AChE and BChE when complexed with the well-known cholinesterase inhibitors RIV [66,67] and galantamine [68][69][70][71] and other ligands with great structural variability, including alkaloids [69,70], carbamates [67], 4-[(alkoxycarbonyl)amino]benzoates [66], and N-benzyl-2-phenylethanamine derivatives [72].…”

Section: Molecular Modeling Studiesmentioning

confidence: 99%

“…These derivatives represent the most and the least active compounds of the whole series. For comparison, we have also included a spatial view of RIV in this figure; the data for the coordinates of this molecule were taken from our previously reported article [66]. It is evident that compound 5d interacts with active site residues in a com- Histogram of interaction energies partitioned with respect to BChE amino acid sequence when complexed with compounds 5c (blue) and 5e (red) overlaid for comparison.…”

Section: Figurementioning

confidence: 99%

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Novel Sulfonamide-Based Carbamates as Selective Inhibitors of BChE

Magar

Parravicini

Štěpánková

et al. 2021

IJMS

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A series of 14 target benzyl [2-(arylsulfamoyl)-1-substituted-ethyl]carbamates was prepared by multi-step synthesis and characterized. All the final compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and the selectivity index (SI) was determined. Except for three compounds, all compounds showed strong preferential inhibition of BChE, and nine compounds were even more active than the clinically used rivastigmine. Benzyl {(2S)-1-[(2-methoxybenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate (5k), benzyl {(2S)-1-[(4-chlorobenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate (5j), and benzyl [(2S)-1-(benzylsulfamoyl)-4-methylpentan-2-yl]carbamate (5c) showed the highest BChE inhibition (IC50 = 4.33, 6.57, and 8.52 µM, respectively), indicating that derivatives 5c and 5j had approximately 5-fold higher inhibitory activity against BChE than rivastigmine, and 5k was even 9-fold more effective than rivastigmine. In addition, the selectivity index of 5c and 5j was approx. 10 and that of 5k was even 34. The process of carbamylation and reactivation of BChE was studied for the most active derivatives 5k, 5j. The detailed information about the mode of binding of these compounds to the active site of both BChE and AChE was obtained in a molecular modeling study. In this study, combined techniques (docking, molecular dynamic simulations, and QTAIM (quantum theory of atoms in molecules) calculations) were employed.

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“…using AMBER analysis tools [19] and PyMOL [39]. This procedure was similar to that previously reported in the reference [40].…”

mentioning

confidence: 93%

Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation

et al. 2020

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Neurodegenerative diseases in which the decrease of the acetylcholine is observed are growing worldwide. In the present study, a series of new arylaminopropanone derivatives with N-phenylcarbamate moiety (1–16) were prepared as potential acetylcholinesterase and butyrylcholinesterase inhibitors. In vitro enzyme assays were performed; the results are expressed as a percentage of inhibition and the IC50 values. The inhibitory activities were compared with reference drugs galantamine and rivastigmine showing piperidine derivatives (1–3) as the most potent. A possible mechanism of action for these compounds was determined from a molecular modelling study by using combined techniques of docking, molecular dynamics simulations and quantum mechanics calculations.

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Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts

Cited by 11 publications

References 39 publications

Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications

Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications

Novel Sulfonamide-Based Carbamates as Selective Inhibitors of BChE

Arylaminopropanone Derivatives as Potential Cholinesterase Inhibitors: Synthesis, Docking Study and Biological Evaluation

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