• MeSH
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• krysa rodu rattus MeSH
• organofosforové sloučeniny toxicita   MeSH
• Check Tag
• krysa rodu rattus MeSH

• MeSH
• acetylcholinesterasa analýza   metabolismus   MeSH
• cholinesterasové inhibitory MeSH
• cykloheximid MeSH
• experimenty na zvířatech MeSH
• hlava účinky záření   MeSH
• krysa rodu rattus MeSH
• mozek enzymologie   účinky záření   MeSH
• radiační účinky MeSH
• Check Tag
• krysa rodu rattus MeSH

• MeSH
• acetylcholinesterasa izolace a purifikace   MeSH
• cholinesterasové inhibitory MeSH
• cholinesterasy izolace a purifikace   MeSH
• experimenty na zvířatech MeSH
• fenothiaziny MeSH
• histocytochemie metody   MeSH
• krysa rodu rattus MeSH
• srdeční síně enzymologie   MeSH
• techniky in vitro MeSH
• Check Tag
• krysa rodu rattus MeSH

Tacrine was the first drug to be approved for Alzheimer's disease (AD) treatment, acting as a cholinesterase inhibitor. The neuropathological hallmarks of AD are amyloid-rich senile plaques, neurofibrillary tangles, and neuronal degeneration. The portfolio of currently approved drugs for AD includes acetylcholinesterase inhibitors (AChEIs) and N-methyl-d-aspartate (NMDA) receptor antagonist. Squaric acid is a versatile structural scaffold capable to be easily transformed into amide-bearing compounds that feature both hydrogen bond donor and acceptor groups with the possibility to create multiple interactions with complementary sites. Considering the relatively simple synthesis approach and other interesting properties (rigidity, aromatic character, H-bond formation) of squaramide motif, we combined this scaffold with different tacrine-based derivatives. In this study, we developed 21 novel dimers amalgamating squaric acid with either tacrine, 6-chlorotacrine or 7-methoxytacrine representing various AChEIs. All new derivatives were evaluated for their anti-cholinesterase activities, cytotoxicity using HepG2 cell line and screened to predict their ability to cross the blood-brain barrier. In this contribution, we also report in silico studies of the most potent AChE and BChE inhibitors in the active site of these enzymes.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• chinin analogy a deriváty   chemie   farmakologie   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• kinetika MeSH
• lidé MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• takrin chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Biogenic metal nanoparticles owing to elimination of hazardous chemicals are beneficial for human healthy and biomedical applications. Considerable properties of these particles have motivated researchers to develop of the biosynthesized nanomaterials. In this study, the gold nanoparticles using Dracocephalum kotschyi leaf extract (d-GNPs) were synthesized and characterized by TEM-SEAD, SEM-EDAX, XRD, Zeta potential, DLS, and FT-IR analysis. TEM photograph showed spherical morphologies with an average size of 11 nm. SEAD pattern authorized fcc structure of these particles. The average zeta value of −29.3 mV revealed the surface charge of green synthesized GNPs. We studied the influence of different parameters such as reaction temperature, contact time, and pH on the synthesis of d-GNPs by UV-vis spectroscopy. Moreover, the obtained nanoparticles were evaluated regarding their biological activity (anti-cholinesterase and anticancer), as well as their influence on both the Gram classes of bacteria. The AuNPs showed an excellent inhibitory efficacy against AChE and BChE. Biological results exhibited that these particles displayed a dose-dependent cytotoxicity with IC50: 196.32 and 152.16 μg/ml against K562 and HeLa cell lines as well. These metal nanoparticles were found to show no activity toward tested bacteria.

• MeSH
• antibakteriální látky farmakologie   MeSH
• antitumorózní látky farmakologie   MeSH
• buňky K562 účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• HeLa buňky účinky léků   MeSH
• hluchavkovité * MeSH
• kovové nanočástice * MeSH
• krystalografie rentgenová MeSH
• listy rostlin MeSH
• rostlinné extrakty MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• transmisní elektronová mikroskopie MeSH
• velikost částic MeSH
• zlato MeSH
• Publikační typ
• práce podpořená grantem MeSH

Acetylcholinesterase (AChE) reactivators (oximes) are generally used as antidotes in case of nerve agent poisoning. Because of their affinity to AChE, they may also act as weak inhibitors of AChE. Their inhibition potency against AChE was determined by an in vitro method based on the interaction between AChE and oxime reactivator in the concentration range 10-1 to 10 -8 M. We used eel AChE for these assays. We found that AChE inhibition strongly depends on the oxime structure. The aim of the present study is to describe the structure-activity relationship (SAR) between oxime structure and inhibition of AChE. AChE reactivators tested include both monoquaternary and bisquaternary structures with the oxime group in different positions on the pyridine ring and with changes in the connecting linker in the case of the bisquaternary compounds. We found AChE inhibition to be highest in bisquaternary oximes that have a longer linker length and have the oxime group in the ortho position. Increased AChE inhibition in monoquaternary oximes was highest when the meta position was occupied by the oxime nucleophile. In addition, different substituents in the connecting chain (in case of bisquaternary oximes) modulated their inhibition potency.

• MeSH
• acetylcholinesterasa metabolismus   účinky léků   MeSH
• antidota farmakologie   MeSH
• cholinesterasové inhibitory otrava   MeSH
• financování organizované MeSH
• lidé MeSH
• molekulární modely MeSH
• oximy farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH

Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. However, oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. The goal of the present study is to determine how oxime structure influences the inhibition of human recombinant AChE (hrAChE). Therefore, 24 structurally different oximes were tested and the results compared to the previous eel AChE (EeAChE) experiments. Structural factors that were tested included the number of pyridinium rings, the length and structural features of the linker, and the number and position of the oxime group on the pyridinium ring.

• MeSH
• acetylcholinesterasa chemie   MeSH
• cholinesterasové inhibitory chemie   MeSH
• katalytická doména MeSH
• lidé MeSH
• oximy chemie   MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• vodíková vazba MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

As part of our efforts to develop sustainable drugs for Alzheimer's disease (AD), we have been focusing on the inexpensive and largely available cashew nut shell liquid (CNSL) as a starting material for the identification of new acetylcholinesterase (AChE) inhibitors. Herein, we decided to investigate whether cardanol, a phenolic CNSL component, could serve as a scaffold for improved compounds with concomitant anti-amyloid and antioxidant activities. Ten new derivatives, carrying the intact phenolic function and an aminomethyl functionality, were synthesized and first tested for their inhibitory potencies towards AChE and butyrylcholinesterase (BChE). 5 and 11 were found to inhibit human BChE at a single-digit micromolar concentration. Transmission electron microscopy revealed the potential of five derivatives to modulate Aβ aggregation, including 5 and 11. In HORAC assays, 5 and 11 performed similarly to standard antioxidant ferulic acid as hydroxyl scavenging agents. Furthermore, in in vitro studies in neuronal cell cultures, 5 and 11 were found to effectively inhibit reactive oxygen species production at a 10 μM concentration. They also showed a favorable initial ADME/Tox profile. Overall, these results suggest that CNSL is a promising raw material for the development of potential disease-modifying treatments for AD.

• Publikační typ
• časopisecké články MeSH

A new benzyldihydroisoquinoline alkaloid (1) was isolated from the tubers of Corydalis cava and named corylucinine. Additionally, 8-trichloromethyl-7,8-dihydropalmatine (2), an isolation artifact of tetrahydropalmatine, was obtained. The structures were established by spectroscopic (including 2D NMR and optical rotation) and HR-ESI-MS methods. Both compounds were tested for human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity. In comparison with the used standards, both compounds showed only moderate inhibitory activity against HuAChE (IC50,. HuAChE = 127.6 +/- 5.2 microM for 1, and IC50, HuAChE = 82.9 +/- 3.9 microM for 2) and none against HuBuChE.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• aktivace enzymů účinky léků   MeSH
• alkaloidy chemie   farmakologie   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory chemie   farmakologie   MeSH
• cholinesterasy metabolismus   MeSH
• Corydalis chemie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Ellman's method is a standard protocol for the determination of cholinesterases activity. Though the method is ready for laboratory purposes, it has some drawbacks as well. In the current article, 2,6-dichloroindophenol acetate is performed as a chromogenic substrate suitable for acetylcholinesterase (AChE) activity examination. Michaelis constant and maximal velocity for 2,6-dichloroindophenol acetate were determined (38.0 µM and 244 pkat) and compared to the values for acetythiocholine (K(m) 0.18 mM; V(max) 5.1 nkat). Docking for 2,6-dichloroindophenol acetate and human AChE was done as well. In conclusion, 2,6-dichloroindophenol acetate seems to be suitable chromogenic substrate for AChE and spectrophotometry and based on this it can be easily performed whenever AChE activity should be tested.

• MeSH
• 2,6-dichlorindofenol chemická syntéza   chemie   farmakologie   MeSH
• acetáty chemická syntéza   chemie   farmakologie   MeSH
• acetylcholinesterasa metabolismus   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH