Tyrosol 1,2,3-triazole analogues as new acetylcholinesterase (AChE) inhibitors

Bousada, Guilherme Mateus; Sousa, Bianca Lana de; Furlani, Gabriela Milane; Agrizzi, Ana Paula; Ferreira, Patrícia Rodrigues; Leite, João Paulo Viana; Mendes, Tiago Antônio de Oliveira; Varejão, Eduardo Vinícius Vieira; Pilau, Eduardo Jorge; Santos, Marcelo Henrique dos

doi:10.1016/j.compbiolchem.2020.107359

Cited by 11 publications

(12 citation statements)

References 44 publications

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“…Additionally, van der Waals interactions were noted between compound 9 and residues ILE-275, ASP-276 and ILE-287. The involvement of the mentioned residues from the AS, AP, and PAS was confirmed to contribute stability to the complex between AChE and synthetic inhibitors such as coumarin-triazole-amino acid hybrids [ 55 ], tyrosol 1,2,3-triazole analogs [ 56 ], coumarin-3-carboxamide-N-morpholine hybrids [ 57 ], chromone derivatives [ 28 ], and chromenyl coumarate [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

et al. 2022

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Coumarin derivatives have been reported as strong antifungal agents against various phytopathogenic fungi. In this study, inhibitory effects of nine coumarinyl Schiff bases were evaluated against the plant pathogenic fungi (Fusarium oxysporum f. sp. lycopersici, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiourum). The compounds were demonstrated to be efficient antifungal agents against Macrophomina phaseolina. The results of molecular docking on the six enzymes related to the antifungal activity suggested that the tested compounds act against plant pathogenic fungi, inhibiting plant cell-wall-degrading enzymes such as endoglucanase I and pectinase. Neither compound exhibited inhibitory effects against two beneficial bacteria (Bacillus mycoides and Bradyrhizobium japonicum) and two entomopathogenic nematodes. However, compound 9 was lethal (46.25%) for nematode Heterorhabditis bacteriophora and showed an inhibitory effect against acetylcholinesterase (AChE) (31.45%), confirming the relationship between these two activities. Calculated toxicity and the pesticide-likeness study showed that compound 9 was the least lipophilic compound with the highest aquatic toxicity. A molecular docking study showed that compounds 9 and 8 bind directly to the active site of AChE. Coumarinyl Schiff bases are promising active components of plant protection products, safe for the environment, human health, and nontarget organisms.

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Section: Resultsmentioning

confidence: 99%

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

et al. 2022

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“…Costimentally, acetylcholine levels in the synaptic process of AD patients are decreased, which causes reduced cortical cholinergic neurotransmission. AChE inhibition becomes a promising therapeutic approach by propitiating a decrease in the rate of acetylcholine hydrolysis, causing an increase in acetylcholine activity in the synaptic cleft and a cognitive improvement with an increase in central cholinergic function [37]. In light of this, products from natural sources have proven attractive for studies aimed at the treatment of AD because they provide milder side effects at therapeutic doses and thus may contribute to overcoming limitations, high hepatoxicity, and low bioavailability of drugs that are already used in AD therapeutics [38,39].…”

Section: Grooming Numbermentioning

confidence: 99%

“…Molecular docking is a technique usually applied in the computational prediction of possible intermolecular interaction modes between a molecule, the ligand, and its receptor [37]. Through docking calculations, it was possible to detect considerable interactions between carvacrol, thymol, and p-cymene with AChE due to the ΔG and Full-Fitness energy values being on a negative scale, which denotes affinity that the molecules exhibit for the E20 and NAG protein regions, as well as the spontaneity of the interaction with these sites.…”

Section: Grooming Numbermentioning

confidence: 99%

Essential Oil of <em>Lippia origanoides</em> H.B.K.: A Promising Compound Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease

Rodrigues¹,

Santos²,

Machado³

et al. 2021

Preprint

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Alzheimer's disease is characterized by a progressive decline of cognitive functions. The class of drugs used for the treatment are acetylcholinesterase inhibitors. Essential oils have contributed to folk medicine and discovery of new drugs for a long time. The purpose of the study was to investigate the in vitro and in silico the anti-acetylcholinesterase activity, as well as acute toxicity of the essential oil of Lippia origanoides. EOLO was obtained by hydrostelting and analyzed by gas chromatography-mass spectrometry. The inhibition assay of acetylcholinesterase enzyme activity was evaluated in vitro, as well as in silico by docking. The effects of EOLO on hematological, biochemical and behavioral parameters were analyzed in mices. We expose that EOLO shows good anti-acetylcholinesterase activity and low toxicity, possibly resulting from the action of the majority compounds thymol, carvacrol and p-cymene. The anti-acetylcholinesterase potential in vitro demonstrating a 70% inhibition. The docking results elucidated the participation of the major phenolics in AChE inhibition by interacting with the catalytic cavity of AchE. The acute oral toxicity test classified as low toxicity. These results contribute to expand the knowledge about essential oil of Lippia origanoides. Therefore, appears to be promising for herbal medicine production with anti-acetylcholinesterase and antioxidant activity.

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“…The 1,2,4-triazoles constitute a class of agrochemicals comprising several compounds widely used as herbicides or fungicides. , Despite the efficiency in controlling weeds and phytopathogens in several crops, the presence of residues of these compounds in food and in the environment constitutes a serious risk to human and animal health. For instance, triazole pesticides are associated with liver, kidney damage, endocrine, nervous system disorders, and carcinogenicity. ,, Such ecotoxicological behavior has led government agencies in several countries to impose strict regulations on the concentrations of residues in the environment and food. , In contrast, the 1,2,3-triazole ring is a pharmacophoric group regarded as a key structural moiety in a range of compounds with medicinally relevant bioactivities, such as antiproliferative, , antileishmanial, , fungicide, and anti -acetylcholinesterase (AChE) activities. , Moreover, a few studies have reported that compounds presenting the 1,2,3-triazole ring have phytotoxic activity. ,, …”

Section: Introductionmentioning

confidence: 99%

“… a (a) Triazole ring system linked to the alkyl chain of tyrosol ( 3–17 ) . (b) Triazole ring system linked built at the phenolic hydroxyl of tyrosol (19–25).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Tyrosol 1,2,3-Triazole Derivatives and Their Phytotoxic Activity against Euphorbia heterophylla

Franco

Silva

Dias

et al. 2022

J. Agric. Food Chem.

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The synthesis and phytotoxic activity of a series of tyrosol 1,2,3-triazole derivatives are reported herein. Target compounds were synthesized through the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), known as click reaction, and these were tested for phytotoxic activity on leaves of wild poinsettia (Euphorbia heterophylla), fleabane (Conyza sumatrensis), and tropical spiderwort (Commelina benghalensis). These are three highly noxious agricultural weeds that challenge available weed control methods, including the use of chemical herbicides. Twenty-five compounds were synthesized and tested. None of the compounds showed phytotoxic activity against C. benghalensis and C. sumatrensis, but almost all of them produced yellowing, bleaching, and necrosis on leaves of E. heterophylla. Two of the tyrosol 1,2,3-triazole derivatives produced more extensive lesions than those produced by the commercial herbicide diquat, used as a positive control (p ≤ 0.05). When applied on leaves of E. heterophylla, these compounds interfered with the stomatal conductance, net photosynthesis, internal carbon concentration, transpiration rate, water-use efficiency, and chlorophyll A and B contents. The interference of such compounds on such photosynthesis-related variables indicates that tyrosol 1,2,3-triazole derivatives may be capable of lowering the competitiveness of E. heterophylla and acting as additional tools for managing this competitive weed in agricultural lands.

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Tyrosol 1,2,3-triazole analogues as new acetylcholinesterase (AChE) inhibitors

Cited by 11 publications

References 44 publications

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

Effects of Coumarinyl Schiff Bases against Phytopathogenic Fungi, the Soil-Beneficial Bacteria and Entomopathogenic Nematodes: Deeper Insight into the Mechanism of Action

Essential Oil of <em>Lippia origanoides</em> H.B.K.: A Promising Compound Acetylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disease

Synthesis of Tyrosol 1,2,3-Triazole Derivatives and Their Phytotoxic Activity against Euphorbia heterophylla

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