The lipophilicity of thirty-two novel acetylcholinesterase (AChE) inhibitors — 1,2,3,4-tetrahydroacridine and 2,3-dihydro-1H-cyclopenta[b]quinoline derivatives was studied by thin layer chromatography. The analyzed compounds were chromatographed on RP-18, RP-8, RP-2, CN and NH2 stationary phases with dioxane — citric buffer pH 3.0 binary mobile phases containing different proportions of dioxane. RM values for pure water were extrapolated from the linear Soczewiński-Wachtmeister equation and six compounds with known literature log P values were used as reference calibration data set for computation of experimental log P values. The obtained results were compared with computationally calculated partition coefficients values (AlogPs, AClogP, AlogP, MlogP, KOWWIN, XlogP2, XlogP3) by PCA and significant differences between them were observed.
defect in the cholinergic system,
enhancement of ACh levels in the brain by in-
hibiting the enzyme acetylcholinesterase (AChE)
was proposed as an important therapeutic ap-
proach. Improving the cholinergic function in AD
patients thus became the neurobiological aim for
treatment (Perry, 1986).
The therapeutic potential of compounds from
natural origin has been successfully demonstrated
in the fi eld of AD; e.g., galanthamine (Fig. 1), a
selective, reversible competitive AChEinhibitor,
is a natural product occurring in the Amaryl-
lidaceae family (Marco and
promising target for anti-AD agents due to its pivotal role in the termination of signal transmission in the cholinergic system through the hydrolysis of ACh [ 7 ], [ 8 ], [ 9 ], [ 10 ]. According to cholinergic hypothesis, the decreased level of ACh results in impairment of the cholinergic neurotransmission leading to the loss of intellectual abilities [ 11 ]. As a result, the design of AChEinhibitors on the basis of the cholinergic hypothesis is still the most popular strategy to identify potent anti-AD drug candidates [ 4 ]. Chalcones have come into prominence as
molecules on enzyme-inhibitor interactions. Using kinetic
studies we discovered that detergents alter the enzy-
matic activity of AChE through an uncompetitive mecha-
nism. Additional experiments using AChEinhibitors
(amphiphilic procaine hydrochloride, hydrophobic tetra-
butylammonium bromide) in the absence or presence of
detergent further illustrate the detergent-enzyme-solvent
interactions. The results contribute to the understanding
of the importance of hydrophobic-lipophilic interactions
for the correct function of AChE and its inhibitors. We
, elevation of acetylcholine levels via AchE inhibition has been accepted as the most effective treatment strategy against AD [ 8 ]. Cholinesterase inhibitors that are selective and free of dose-limiting side effects are not currently available. In addition, some of the synthetic drugs used, such as donepezil and rivastigmine, have been reported to cause gastrointestinal disturbances in addition to their poor bioavailability [ 9 ], [ 10 ]. Hence, the search for new AchEinhibitors, particularly from natural products resources, with better efficacy and lower side effects is
treatment of AD [ 7 ]. Acetylcholinesterase enzyme (AChE) are mainly presented in the central nervous system, catalyze the hydrolysis of neurotransmitter acetylcholine (ACh) to choline. ACh deficiency was noted in Alzheimer patients, which have been proposed in cholinergic theory [ 8 ]. Galantamine and rivastigmine, two AChEinhibitor drugs which isolated from medicinal plants, have been licensed for the treatment of AD, but they have several adverse reactions [ 9 ]. Therefore, some studies have screened medicinal plants toward isolation and identification of AChE
formation of an
acetylcholinesterase (AChE)-inhibiting oxo analog of coumaphos was verified and con-
firmed by laser flash photolysis.
The suitability of bioanalytical flow-injection analysis (FIA) systems, based on AChE
inhibition and spectrophotometric or thermal lens spectrometric detection for rapid and sen-
sitive screening in food quality control was demonstrated. Owing to the high sensitivity of
thermal lens spectrometry (TLS), several steps in sample preparation can be avoided (pre-
concentration, purification, isolation) and incubation times reduced. High sample
Natural products are the inspiration for many valuable therapeutic agents and attest to biodiversity being a rich source of new molecular structures. Their value as templates for medicinal chemistry remains undisputed, even after the growth of the combinatorial chemistry era. Tropical environments, such as Brazilian biomes, offer a particularly rich potential for biologically active compounds with unique structures and continue to contribute toward modern drug discovery. Our bioprospecting of plant species of the Cerrado and Atlantic Forest biomes has yielded promising bioactive secondary metabolites, and we describe some of these molecules and semisynthetic derivatives as potential acetylcholinesterase (AChE) inhibitors.
Enzyme inhibitors play a significant role in the drug discovery process. For instance, acetylcholinesterase (AChE) inhibitors have applications in curing Alzheimer’s disease (AD), senile dementia, ataxia, myasthenia gravis, and Parkinson’s disease. Glutathione S-transferase (GST) inhibitors have applications as adjuvants to overcome anticancer and antiparasitic drug resistance problems. Compounds inhibiting the activity of α-glucosidase are used to treat type 2 diabetes mellitus and obesity problems. This article describes the identification of natural products exhibiting AChE, GST, and α-glucosidase inhibitory activities from medicinally important plants. Additionally, structure–activity relationship (SAR) studies of these newly discovered enzyme inhibitors are also discussed.