Discovery and Structure–Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening

Dighe, Satish N.; Deora, Girdhar Singh; Mora, E. De la; Nachon, Florian; Chan, Stephen; Parat, Marie-Odile; Brazzolotto, Xavier; Ross, Benjamin P.

doi:10.1021/acs.jmedchem.6b00356

Cited by 125 publications

(86 citation statements)

References 41 publications

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“…The inhibitory activity of the selected EOs on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) cholinesterase (ChE) were studied since these enzymes have a fundamental role in the nervous system, as they are responsible for the hydrolysis of ACh [87]. L. officinalis and M. pulegium EOs, both rich in oxygenated terpenes, showed the highest inhibitory potency on AChE.…”

Section: Discussionmentioning

confidence: 99%

Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants

et al. 2020

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In this study, the essential oils (EOs) of six Algerian plants (Artemisia campestris L., Artemisia herba-alba Asso, Juniperus phoenicea L., Juniperus oxycedrus L., Mentha pulegium L. and Lavandula officinalis Chaix) were obtained by hydrodistillation, and their compositions determined by GC-MS and GC-FID. The antioxidant activity of the EOS was evaluated via 2,2′-diphenyl-1-picrylhydrazyl (DPPH), ferric-reducing/antioxidant power (FRAP) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Moreover, their cytotoxic effect was evaluated—as well as their tyrosinase, acetyl- and butyryl-cholinesterase (AChE and BuChE) inhibitory activities. The chemical analyses detected 44, 45, 51, 53, 26 and 40 compounds in EOs of A. campestris, A. herba-alba, J. phoenicea, J. oxycedrus, M. pulegium and L. officinalis, respectively. A. campestris EO was mainly composed of β-pinene (20.7%), while A. herba-alba EO contained davanone D (49.5%) as the main component. α-Pinene (41.8%) was detected as the major constituent in both J. phoenicea (41.8%) and J. oxycedrus (37.8%) EOs. M. pulegium EO was characterized by pulegone as the most abundant (76.9%) compound, while linalool (35.8%) was detected as a major constituent in L. officinalis EO. The antioxidant power evaluation revealed IC50 values ranging from 2.61 to 91.25 mg/mL for DPPH scavenging activity, while the FRAP values ranged from 0.97–8.17 µmol Trolox equivalents (TX)/g sample. In the ABTS assay, the values ranged from 7.01 to 2.40 µmol TX/g sample. In the presence of 1 mg/mL of the samples, tyrosinase inhibition rates ranged from 11.35% to 39.65%, AChE inhibition rates ranged from 40.57% to 73.60% and BuChE inhibition rates ranged from 6.47% to 72.03%. A significant cytotoxic effect was found for A. herba-alba EO. The obtained results support some of the traditional uses of these species in food preservation and for protection against several diseases.

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Section: Discussionmentioning

confidence: 99%

Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants

et al. 2020

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“…In the study of Wu et al, synthetic compounds showed similar effectiveness in inhibiting BuChE from equine and human plasma, but with a higher potency over the human enzyme [39]. Similarly, Dighe et al have shown that their lead was 2-fold more potent in inhibiting human BuChE than equine BuChE [40]. In the same way, we could hope for a better activity in human BuChE.…”

Section: Characterization Of the Active Pharmaceutical Ingredient (Api)mentioning

confidence: 91%

Pharmacotechnical Development of a Nasal Drug Delivery Composite Nanosystem Intended for Alzheimer’s Disease Treatment

et al. 2020

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Direct nose-to-brain delivery has been raised as a non-invasive powerful strategy to deliver drugs to the brain bypassing the blood-brain barrier (BBB). This study aimed at preparing and characterizing an innovative composite formulation, associating the liposome and hydrogel approaches, suitable for intranasal administration. Thermosensitive gel formulations were obtained based on a mixture of two hydrophilic polymers (Poloxamer 407, P407 and Poloxamer 188, P188) for a controlled delivery through nasal route via liposomes of an active pharmaceutical ingredient (API) of potential interest for Alzheimer’s disease. The osmolarity and the gelation temperature (T° sol-gel) of formulations, defined in a ternary diagram, were investigated by rheometry and visual determination. Regarding the issue of assays, a mixture composed of P407/P188 (15/1%, w/w) was selected for intranasal administration in terms of T° sol-gel and for the compatibility with the olfactory mucosal (280 ± 20 mOsmol, pH 6). Liposomes of API were prepared by the thin film hydration method. Mucoadhesion studies were performed by using mucin disc, and they showed the good natural mucoadhesive characteristics of in situ gel formulations, which increased when liposomes were added. The study demonstrated successful pharmacotechnical development of a promising API-loaded liposomes in a thermosensitive hydrogel intended for nasal Alzheimer’s disease treatment.

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“…Among these, donepezil and galantamine are selective AChE inhibitors, while rivastigmine is a dual AChE-BuChE-inhibiting compound. 17 The active site of human AChE is a long gorge with a length of approximately 20Å. Two key sites, namely the catalytic active site (CAS) at the bottom of the gorge and the peripheral anionic site (PAS) near the entrance of the gorge, are linked by a narrow groove.…”

Section: Introductionmentioning

confidence: 99%

Discovery of new acetylcholinesterase and butyrylcholinesterase inhibitors through structure-based virtual screening

et al. 2017

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Discovery and Structure–Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening

Cited by 125 publications

References 41 publications

Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants

Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants

Pharmacotechnical Development of a Nasal Drug Delivery Composite Nanosystem Intended for Alzheimer’s Disease Treatment

Discovery of new acetylcholinesterase and butyrylcholinesterase inhibitors through structure-based virtual screening

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