Synthesis of Novel Benzimidazole and Benzothiazole Derivatives Bearing a 1,2,3-triazole Ring System and their Acetylcholinesterase Inhibitory Activity

2017 ◽  
Vol 41 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Laleh Faraji ◽  
Shiva Shahkarami ◽  
Hamid Nadri ◽  
Alireza Moradi ◽  
Mina Saeedi ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Docking Simulation ◽  
Triazole Ring ◽  
Copper Catalysts ◽  
Inhibitory Effect ◽  
Ring System ◽  
Benzothiazole Derivatives ◽  
Ache Inhibitory Activity ◽  
Group A

A series of 20 novel benzimidazole and benzothiazole derivatives linked to a 1,2,3-triazole ring system was synthesised, characterised and evaluated for in vitro acetylcholinesterase (AChE) inhibitory activity. Several copper catalysts and solvents were screened to establish the optimal conditions for the preparation of the target compounds. Three different linkers were used to optimise the enzyme inhibitory effect. Out of the 20 compounds, 13 showed some AChE inhibition. The most potent compound, which showed 84% inhibition at 100 μM, contained a 1-(2-fluorobenzyl)-1,2,3-triazole linked to a benzimidazole group. A docking simulation study showed that the most active compound bound preferentially to the catalytic anionic subsite of the AChE enzyme.

scholarly journals Development of mouthwash with Rosmarinus officinalis extract

2014 ◽  
Vol 50 (4) ◽  
pp. 851-858 ◽  
Author(s):  
Isabela Moreira Baumgratz de Paula ◽  
Flávia Costa Moraes ◽  
Orlando Vieira de Souza ◽  
Célia Hitomi Yamamoto
Keyword(s):  
Sodium Fluoride ◽  
Inhibitory Activity ◽  
Raw Materials ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Rosmarinus Officinalis ◽  
Hexane Fraction ◽  
Diffusion Method ◽  
Oral Infections

Rosmarinus officinalis, which belongs to the Lamiaceaefamily, is a species of medicinal flora with therapeutic properties. In order to exploit the benefits of these properties, a mouthwash formulation was developed, with careful selection of raw materials to meet pharmacotechnical requirements. Extracts of the plant were incorporated into a mouthwash, which was shown to have inhibitory action in vitro against the micro-organisms commonly found in periodontics. Controls for assessing the quality of the drugs were carried out, quantifying phenols and flavonoids as chemical markers. Mouthwash solutions were formulated containing 0.1, 5 and 10% ethanol extract of R. officinalis; and 0.05, 5 and 10% of the hexane fraction of R. officinalis. In order to evaluate synergism, ethanol extract and hexane fraction were also added to formulations containing 0.05% sodium fluoride and 0.12% chlorhexidine digluconate. These formulations were assessed for inhibitory effect against the specific microorganisms involved in the process of bacterial plaque formation, S. mutans(ATCC25175) and C. albicans(ATCC 10231), frequently found in cases of oral infections. The agar diffusion method was used to evaluate the inhibitory activity of extracts and formulations. All mouthwash solutions displayed inhibitory activity having higher sensitivity to S. mutansfor the 5% ethanol extract+0.05% sodium fluoride, and greater sensitivity to C. albicansfor the 10% hexane fraction. Results were characterized by the appearance of a growth inhibition halo, justifying the utilization and association of extracts of R. officinalis.

scholarly journals In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

2013 ◽  
Vol 49 (4) ◽  
pp. 803-809
Author(s):  
Monica Lacerda Lopes Martins ◽  
Henrique Poltronieri Pacheco ◽  
Iara Giuberti Perini ◽  
Dominik Lenz ◽  
Tadeu Uggere de Andrade ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Colorimetric Assay ◽  
Hypotensive Effect ◽  
Ace Inhibition ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Total Phenolic ◽  
Before And After

In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES), a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE) activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE) and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg), with acetylcholine (ACh) as positive control (5 µg/kg, i.v.). The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg) in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.). Captopril (30 mg/kg) was used as positive control. Bulbostylis capillaris (86.89 ± 15.20%) and ERE (74.89 ± 11.95%, ERE) were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%). ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo

Fitoterapia ◽  
2016 ◽  
Vol 110 ◽  
pp. 142-149 ◽  
Author(s):  
Heng-Wen Chen ◽  
Xuan-Hui He ◽  
Rong Yuan ◽  
Ben-Jun Wei ◽  
Zhong Chen ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Valeriana Officinalis ◽  
Ache Inhibitory Activity

IN VITRO STUDIES OF SOME EDIBLE SPICES ON PANCREATIC LIPASE INHIBITORY ACTIVITY

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 62-68
Author(s):  
S Mhatre ◽  
◽  
A. Bhagit ◽  
R. P Yadav
Keyword(s):  
Pancreatic Lipase ◽  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Syzygium Aromaticum ◽  
High Potency ◽  
Good Source ◽  
Zanthoxylum Armatum ◽  
Methanolic Extracts ◽  
Cinnamomum Tamala

Pancreatic lipase inhibitory effect of some edible spices in light of percent inhibition, efficacy, reversibility/ irreversibility and effect of pH on inhibition is presented here. Lipase inhibitory activities of methanolic extracts of eighteen spices were evaluated. Extracts of Zanthoxylum armatum, Cinnamomum tamala, Syzygium aromaticum and Myristica fragrans were considered to be of high potency in synthetic substrate assay. Only Syzygium aromaticum showed high potency in natural substrate based lipase assay. Zanthoxylum armatum extract displayed lowest IC50 of 9.0 μg/mL. On dialysis, all extracts lost their lipase inhibitory activity indicating reversible nature of inhibition. pH significantly affected the performance of spice extracts during inhibition of pancreatic lipase. Most of the extracts lost their pancreatic lipase inhibitory activity at pH 3.0 with the exception of Brassica nigra and Cinnamomum tamala. Results showed spice are good source of pancreatic lipase inhibitor and its potential as drug for obesity can be explored by addressing various issues.

scholarly journals Phenolic Acids from Lycium barbarum Leaves: In Vitro and In Silico Studies of the Inhibitory Activity against Porcine Pancreatic α-Amylase

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1388
Author(s):  
Luna Pollini ◽  
Alessandra Riccio ◽  
Cristina Juan ◽  
Carmela Tringaniello ◽  
Federica Ianni ◽  
...  
Keyword(s):  
Phenolic Acids ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Lycium Barbarum ◽  
Plant Materials ◽  
Vitro Assay ◽  
In Silico Studies

Nowadays, bioactive compounds from vegetable food and waste are of great interest for their inhibitory potential against digestive enzymes. In the present study, the inhibitory activity of methanolic extract from Lycium barbarum leaves on porcine pancreas α-amylase has been studied. The α-amylase inhibitory activity of the constituent phenolic acids was also investigated. The leaves were extracted by ultrasound-assisted method, one of the most efficient techniques for bioactive extraction from plant materials, and then the phenolic acids were identified by Accurate-Mass Quadrupole Time-of-Flight (Q-TOF) Liquid Chromatography/Mass Spectrometry (LC/MS). Chlorogenic and salicylic acids were the most abundant phenolic acids in L. barbarum leaf extract. The inhibitory effect against α-amylase, determined for individual compounds by in vitro assay, was higher for chlorogenic, salicylic, and caffeic acids. L. barbarum leaf extract showed an appreciable α-amylase inhibitory effect in a concentration-dependent manner. Docking studies of the considered phenolic acids into the active site of α-amylase suggested a conserved binding mode that is mainly stabilized through H-bonds and π-π stacking interactions.

scholarly journals Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1215 ◽  
Author(s):  
Jayeong Hwang ◽  
Kumju Youn ◽  
Yeongseon Ji ◽  
Seonah Lee ◽  
Gyutae Lim ◽  
...  
Keyword(s):  
Docking Simulation ◽  
Inhibitory Effect ◽  
Potential Effect ◽  
Van Der Waals Interactions ◽  
Inhibitory Effects ◽  
Computational Docking ◽  
In Silico Docking ◽  
Ic50 Values ◽  
Physiological Benefits

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with IC50 values of 2.74 ± 0.48 µM and 4.12 ± 0.42 µM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood–brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological efficacy in the prevention of AD.

scholarly journals Enhanced efficacy of endonuclease inhibitor baloxavir acid against orthobunyaviruses when used in combination with ribavirin

2020 ◽  
Vol 75 (11) ◽  
pp. 3189-3193
Author(s):  
Sebastiaan ter Horst ◽  
Yaiza Fernandez-Garcia ◽  
Marcella Bassetto ◽  
Stephan Günther ◽  
Andrea Brancale ◽  
...  
Keyword(s):  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Docking Simulation ◽  
Antiviral Effect ◽  
Inhibitory Effect ◽  
Surface Model ◽  
La Crosse Virus ◽  
Endonuclease Domain ◽  
Substrate Cleavage

Abstract Objectives Baloxavir acid is an endonuclease inhibitor approved for use against influenza. We evaluated whether this compound also targets the endonuclease domain of orthobunyaviruses and therefore could potentially be used against orthobunyavirus infections. Methods We performed a thermal shift assay and a fluorescence resonance energy transfer (FRET)-based nuclease monitoring assay using the La Crosse virus (LACV) endonuclease and baloxavir acid to prove their interaction and identify an inhibitory effect. Their interaction was further studied in a docking simulation using Glide SP. We show that baloxavir acid inhibits the viral replication of Bunyamwera virus (BUNV)–mCherry in vitro using high-content imaging and virus yield assay. Lastly, we investigated the use of baloxavir acid in combination with ribavirin in vitro by implementing the Zero Interaction Potency response surface model. Results We show that baloxavir acid augments LACV enzyme’s melting temperature with ΔTm 9.5 ± 0.4°C and inhibited substrate cleavage with IC50 0.39 ± 0.03 μM. Moreover, our docking simulation suggests that baloxavir acid is able to establish an efficient binding with the LACV endonuclease. In the cell-based assay, we observed that baloxavir acid and ribavirin inhibited BUNV–mCherry with an EC50 of 0.7 ± 0.2 μM and 26.6 ± 8.9 μM, respectively. When used in combination, we found a maximum synergistic effect of 8.64. Conclusions The influenza endonuclease inhibitor baloxavir acid is able to bind to and interfere with the endonuclease domain of orthobunyaviruses and yields a more potent antiviral effect than ribavirin against BUNV–mCherry. The combination of both compounds results in a more potent antiviral effect, suggesting that these molecules could potentially be combined to treat orthobunyavirus-infected patients.

scholarly journals Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 10 ◽  
Author(s):  
Hehua Xiong ◽  
Jianxin Cheng ◽  
Jianqing Zhang ◽  
Qian Zhang ◽  
Zhen Xiao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Docking Simulation ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Mcf 7

A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

Synthesis and Biological Evaluation of Acetylcholinesterase Inhibitor Macakurzin C and Its Derivatives

Synlett ◽  
2015 ◽  
Vol 26 (08) ◽  
pp. 1131-1134 ◽  
Author(s):  
Hyoungsu Kim ◽  
Seung-Hoon Baek ◽  
Hongjun Jang
Keyword(s):  
Inhibitory Activity ◽  
Acetylcholinesterase Inhibitor ◽  
Biological Evaluation ◽  
Hydroxyl Groups ◽  
Structural Requirements ◽  
Ache Inhibitory Activity ◽  
Synthesis And Biological Evaluation ◽  
Derivatives Of

The derivatives of macakurzin C containing a modified D ring and protected C(3)/C(5)-hydroxyl groups were synthesized and their in vitro AChE inhibitory activity and neurotoxicity were evaluated to identify the structural requirements for the activities. The results indicated that C(3)-benzyl-protected derivative has a more potent AChE inhibitory activity (IC50, 2.6 μM) and a less neurotoxicity (GI50, >100 μM) than synthetic macakurzin C (IC50, 9.1 μM; GI50, 16.6 μM).

scholarly journals α-Glucosidase Inhibitory Activity of Phenolic Rich Extracts Obtained from the Seeds of Melastoma saigonense (Kuntze) Merr.

2019 ◽  
Vol 31 (12) ◽  
pp. 2964-2968 ◽  
Author(s):  
Nutthamon Prajudtasri ◽  
Mongkol Nontakitticharoen ◽  
Sujint Anguravirutt
Keyword(s):  
Ethyl Acetate ◽  
Inhibitory Activity ◽  
Total Phenolic Content ◽  
Phenolic Content ◽  
Inhibitory Effect ◽  
Total Phenolic ◽  
Phytochemical Analysis ◽  
Antidiabetic Agent ◽  
Seed Extracts

The aim of this study was to perform a phytochemical analysis of Melastoma saigonense seed extracts and to determine their α-glucosidase inhibitory activity. The extracts from seeds of M. saigonense indicated that the total phenolic content was in the range between 233.46 and 967.22 mg GAE/g DE, whereas the flavonoids content was in the range between 359.96 and 850.84 mg QE/g DE. The present study of antidiabetic inhibitory activity by in vitro α-glucosidase revealed that the crude extracts using ethyl acetate (EA), butanol (BU) and final aqueous residue extracts (AQ) exhibited a strong α-glucosidase inhibitory effect (IC50 4.42-11.95 μg/mL). The ethyl acetate and butanol extracts of seeds of Melastoma saigonense (Kuntze) Merr. were further fractionated by silica gel column chromatography into four fractions (EAF1−EAF4) and five fractions (BUF1−BUF5), respectively and their bioactivities were investigated. The nine fractions exhibited significant α-glucosidase inhibitory activity (p < 0.05) with an IC50 between 3.42-34.77 μg/mL which is less than the IC50 for standard acarbose (IC50 = 507.26 μg/mL). Among all the fractions, BUF1 and EAF1 exhibited high inhibitory activity against α-glucosidase with BUF1 showing the highest inhibitory activity (IC50 = 3.42 μg/mL). The dominant phenolic acids were sinapic, gallic, ferrulic, syringic, gallic and caffeic acids and the prominent flavonoids were myricetin and quercetin. These findings suggest that the seeds of M. saigonense have potential as a source of antidiabetic agent (s).

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