Zinc metal carboxylates as potential anti-Alzheimer’s candidate: <i>in vitro</i> anticholinesterase, antioxidant and molecular docking studies

Zafar, Rehman; Zubair, Muhammad; Ali, Saqib; Shahid, Khadija; Waseem, Wajeeha; Naureen, Humaira; Haider, Ali; Jan, Muhammad; Ullah, Farhat; Sirajuddin, Muhammad; Sadiq, Abdul

doi:10.1080/07391102.2020.1724569

Cited by 38 publications

(22 citation statements)

References 18 publications

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“…Antioxidants have been reported to thwart the destruction of β-cells via inhibition of peroxidation chain reaction and consequently offer protection against the development of DM (Montonen, 2005). The antioxidant can be from both organic and inorganic sources (Bibi et al, 2019;Zafar et al, 2020). However, medicinal plants are enriched with natural antioxidants that can protect β-cell function and stop diabetes mediated ROS formation (Sadiq et al, 2015a;Begum et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches

et al. 2020

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Natural-based drugs are believed to be safe, effective and economical. Based on the medicinal importance of the genus Eryngium and unexplored nature of Eryngium caeruleum, we have evaluated its antidiabetic and antioxidant potentials. Both in-vitro and in-vivo assays have been carried out for antidiabetic assays. The antioxidant activity was determined by using different free radicals [i.e., 1,1-diphenyl,2-picrylhydrazyl (DPPH), 2,2-azinobis[3-ethylbenzthiazoline]-6-sulfonic acid (ABTS), and hydrogen peroxide (H2O2)]. Moreover, different phytoconstituents were identified in the most active solvent fraction by GC-MS analysis. Furthermore, comparative fingerprints of methanolic extract and chloroform fraction were also analyzed via High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD). The crude methanolic extract of E. caeruleum (Ec.Cr) and its sub-fractions [i.e., n-hexane (Ec.Hex), chloroform (Ec.Chf), ethyl acetate (Ec.EtAc), and aqueous (Ec.Aq) were employed in this study]. In the α-glucosidase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The most active sample was Ec.Chf which revealed an IC50 of 437 μg/ml in comparison to the standard acarbose (IC50 25 μg/ml). The rest of the samples showed moderate inhibition of α-glucosidase. In antioxidant assays, Ec.Chf and Ec.Cr exhibited a considerable scavenging effect against all the free radicals. The IC50 values recorded for Ec.Chf were 112, 109, and 150 μg/ml against DPPH, ABTS, and H2O2 respectively. Based on the in-vitro potential of Ec.Chf, this was subjected to the in-vivo model experiment. The Ec.Chf lowered the blood glucose level up to 10.3 mmol/L at 500 μg/Kg. The Ec.Chf was also subjected to GC-MS analysis. The GC-MS analysis confirmed the presence of 60 compounds. The identified phytoconstituents consist of some essential compounds previously reported with antidiabetic and antioxidant studies, which include thymol, tocopherol, phytol, nerolidol, (I)-neophytadiene, linolenic acid, and falcarinol. Similarly, the HPLC-DAD chromatograms of Ec.Cr and Ec.Chf exhibited a variety of peaks, which further demonstrates the possibility of important phytochemicals. In a nutshell, we can conclude that Eryngium caeruleum is a potential source of bioactive compounds which may be beneficial for the management of ailments like diabetes and free radicals mediated disorders. Molecular docking was performed to explore the possible role of all the identified bioactive compounds in the chloroform fraction of Eryngium caeruleum into active sites of the homology model of α-glucosidase.

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Section: Introductionmentioning

confidence: 99%

Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches

et al. 2020

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“…1,2 Although the complex pathophysiological aspects of AD are not quite clear, yet numerous therapeutic agents including cholinesterase (AChE/BChE) inhibitors, BACE1 inhibitors, metal chelators, amyloid-β-peptide vaccination, cholesterol-lowering, and anti-inflammatory agents have been tested as potential AD therapeutics. [3][4][5] Acetylcholine is an important neurotransmitter implicated in the communication of impulses across the synapse. [6][7][8] This neurotransmitter is cleared by two vital enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).…”

Section: Introductionmentioning

confidence: 99%

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

Ahmad

Ullah

Sadiq

et al. 2020

DDDT

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Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics. Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC 50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC 50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC 50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC 50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H 2 O 2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2. Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

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“…After successful docking between the selected ligands (set of protease inhibitors) and the binding site of SARS-CoV-2 3CL pro and PL pro , the ligands' docking scores were noted and the best-ranked poses with the lowest docking score were chosen for interaction studies in detail. The mode of interaction of inhibitor compounds with amino acid residues in protein binding sites results in the compounds' binding affinity and potency [Zafar et al, 2020] .…”

Section: Resultsmentioning

confidence: 99%

“Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CLpro and PLpro"

Bhowmik

Sharma

Prakash

et al. 2021

Journal of Molecular Structure

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The sudden increase in the COVID-19 epidemic affected by novel coronavirus 2019 has jeopardized public health worldwide. Hence the necessities of a drug or therapeutic agent that heal SARS-CoV-2 infections are essential requirements. The viral genome encodes a large Polyprotein, further processed by the main protease/ 3C-like protease (3CL pro ) and papain-like proteases (PL pro ) into 16 nonstructural proteins to form a viral replication complex. These essential functions of 3CL pro and PL pro in virus duplication make these proteases a promising target for discovering potential therapeutic candidates and possible treatment for SARS-CoV-2 infection. This study aimed to screen a unique set of protease inhibitors library against 3CL pro and PL pro of the SARS-CoV-2. A molecular docking study was performed using PyRx to reveal the binding affinity of the selected ligands and molecular dynamic simulations were executed to assess the three-dimensional stability of protein-ligand complexes. The pharmacodynamics parameters of the inhibitors were predicted using admetSAR. The top two ligands (Nafamostat and VR23) based on docking scores were selected for further studies. Selected ligands showed excellent pharmacokinetic properties with proper absorption, bioavailability and minimal toxicity. Due to the emerging and efficiency of remdesivir and dexamethasone in healing COVID-19 patients, ADMET properties of the selected ligands were thus compared with it. MD Simulation studies up to 100ns revealed the ligands' stability at the target proteins' binding site residues. Therefore, Nafamostat and VR23 may provide potential treatment options against SARS-CoV-2 infections by potentially inhibiting virus duplication though more research is warranted.

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Zinc metal carboxylates as potential anti-Alzheimer’s candidate: in vitro anticholinesterase, antioxidant and molecular docking studies

Cited by 38 publications

References 18 publications

Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches

Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches

<p>Comparative Cholinesterase, α-Glucosidase Inhibitory, Antioxidant, Molecular Docking, and Kinetic Studies on Potent Succinimide Derivatives</p>

“Identification of Nafamostat and VR23 as COVID-19 drug candidates by targeting 3CLpro and PLpro"

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