Isolation and Characterization of Acetylcholinesterase Inhibitors from Piper longum and Binding Mode Predictions

Planta Medica ◽  
2020 ◽  
Vol 86 (15) ◽  
pp. 1118-1124 ◽  
Author(s):  
Zakie Khatami ◽  
Sonja Herdlinger ◽  
Parisa Sarkhail ◽  
Martin Zehl ◽  
Hanspeter Kaehlig ◽  
...  
Keyword(s):  
Colorimetric Assay ◽  
Therapeutic Option ◽  
Acetylcholinesterase Inhibitors ◽  
Binding Mode ◽  
Rational Approach ◽  
Protein Data Bank Code ◽  
Piper Longum ◽  
Isolation And Characterization ◽  
Inhibitory Activities

AbstractRestoration of cholinergic function is considered a rational approach to enhance cognitive performance. Acetylcholinesterase inhibitors are still the best therapeutic option for Alzheimerʼs disease. The fruits of Piper longum have been used in traditional medicines for the treatment of memory loss. It was demonstrated that the dichloromethane extract of these fruits is able to inhibit acetylcholinesterase. Thus, the aim of this study was to identify the contained acetylcholinesterase inhibitors. The active zones were presented via TLC-bioautography, and five compounds were isolated in the process of a bioassay-guided phytochemical investigation. Their structures were characterized as piperine, methyl piperate, guineenisine, pipercide, and pellitorine using spectroscopy and spectrometry methods (UV, IR, MS, 1H-, and 13C-NMR). In vitro acetylcholinesterase inhibitory activities of the isolates and their IC50 values were determined via a colorimetric assay. Three of them exhibited enzyme inhibitory activities, with piperine being the most potent compound (IC50 of 0.3 mM). In order to investigate the binding mode of the tested compounds, docking studies were performed using the X-ray crystal structure of acetylcholinesterase from Tetronarce californica with the Protein Data Bank code 1EVE. The content of the active compounds in the extract was determined by a developed HPLC method. Piperine was present in the maximum quantity in the fruits (0.57%), whereas methyl piperate contained the minimum content (0.10%).

scholarly journals Cytotoxic Activity of Lomatiol and 7-(3′-Hydroxymethyl-3′-methylallyloxy)coumarin

2016 ◽  
Vol 11 (3) ◽  
pp. 1934578X1601100
Author(s):  
Serena Fiorito ◽  
Salvatore Genovese ◽  
Francesco Epifano ◽  
Veronique Mathieu ◽  
Robert Kiss ◽  
...  
Keyword(s):  
Structural Feature ◽  
Colorimetric Assay ◽  
Parent Compound ◽  
Side Chain ◽  
In Vitro Growth ◽  
Mtt Colorimetric Assay ◽  
Growth Inhibitory ◽  
Inhibitory Activities ◽  
Comparison Data

7-(3′-Hydroxymethyl-3′-methylallyloxy)coumarin, bearing a 3′-hydroxy-3′-methylallyl group as the O-side chain, and lomatiol, a lapachol derivative sharing the same structural feature, were tested for their in vitro growth inhibitory activities on six cancer cell lines using the MTT colorimetric assay, along with the respective 3′,3′-dimethylallyl derivatives and unprenylated products used for comparison. Data revealed that lomatiol displayed the strongest growth inhibitory activities in vitro although not as efficient as the parent compound lapachol. The oxidized O-prenylcoumarin recorded better growth inhibitory capacities than the prenylated and unprenylated parent products.

Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

MedPharmRes ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 15-25
Author(s):  
Dao Tran ◽  
Son Tran ◽  
Vi Nguyen ◽  
Tri Le ◽  
Minh Thai ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Condensation Reaction ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Studies ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Ellman’S Method

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 µM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 µM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

Synthesis, Molecular Docking, and In Vitro Investigation of 1,1'-Diaryl- 3,3'-(p-phenylenedicarbonyl) dithioureas as Urease Inhibitors

2020 ◽  
Vol 17 (4) ◽  
pp. 254-259
Author(s):  
Hummera Rafique ◽  
Fizza Tahira ◽  
Syeda Zar Afshan ◽  
Muhammad Naseem ◽  
Naghmana Kausar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Mode ◽  
Docking Studies ◽  
Inhibitor Binding ◽  
In Vitro Investigation ◽  
Urease Enzyme ◽  
Inhibitory Activities ◽  
Urease Inhibitory ◽  
High Yields

Synthesis of some 1,1'-diaryl-3,3'-(p-phenylenedicarbonyl)dithioureas was accomplished in two steps. Dithioureas were prepared under inert conditions with significantly high yields. Inhibitory activity of dithiourea compounds was investigated against urease enzyme. All the synthesized compounds were evaluated for their urease inhibitory activities, and molecular docking studies were carried out to ascertain the inhibitor binding mode with the enzyme. All the compounds displayed moderate to significant urease inhibitory activities.

Synthesis and Molecular Simulation Studies of Mandelic Acid Peptidomimetic Derivatives as Aminopeptidase N Inhibitors

2020 ◽  
Vol 16 ◽  
Author(s):  
Jiawei Chen ◽  
Qiaoli Lv ◽  
Guogang Tu
Keyword(s):  
Molecular Simulation ◽  
Mandelic Acid ◽  
Critical Role ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Binding Energies ◽  
Aminopeptidase N ◽  
Dynamics Simulation ◽  
Inhibitory Activities

Background: The aminopeptidase N (APN) over-expressed in tumor cells plays a critical role in angiogenesis which makes the development of APN inhibitors an attractive strategy for cancer research. Aims and Objectives: It is clinically significant to develop potential APN inhibitors for cancer treatment. Reported here are the design, synthesis, biological evaluation and molecular simulation of mandelic acid peptidomimetic derivatives as APN inhibitors. Materials and Methods: Analysis of the binding mode of bestatin to APN lead to the design and synthesis of mandelic acid peptidomimetic derivatives. APN inhibitory activities in vitro were evaluated by spectrophotometric method. The binding mode of the target compounds with the APN binding site was studied relying on docking studies, molecular dynamics simulation experiments and binding energies calculation. Results: The structures of target compounds were confirmed by IR, 1H-NMR and MS. All compounds exhibited different range of inhibitory ability with IC50 values lying in micromolar level. The compound 9m was found to be most potent as compared to other target derivatives. Molecular simulation revealed that ligand coordinating with the catalytic zinc ion is very important for inhibitory activities. Conclusion: The compound 9m might represent a promising scaffold for the further development of novel anti-cancer drugs.

scholarly journals Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2-a]Pyrimidines as New Acetylcholinesterase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2306 ◽  
Author(s):  
Mohamed Y. Mahgoub ◽  
Awatef M. Elmaghraby ◽  
Abd-Elfttah A. Harb ◽  
João L. Ferreira da Silva ◽  
Gonçalo C. Justino ◽  
...  
Keyword(s):  
Colorimetric Assay ◽  
Treatment Options ◽  
Acetylcholinesterase Inhibitors ◽  
2D Nmr ◽  
Biological Evaluation ◽  
X Ray Diffraction ◽  
Docking Simulations ◽  
Starting Point ◽  
Ic50 Values

A new series of thiazolo[3,2-a]pyrimidine bromide salt derivatives 7a–d were synthesized from 3,4-dihydropyrimidinethione precursors. The target compounds were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which confirmed a regioselective 5H cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase (hAChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC50 values in the 1 µM range). Molecular docking simulations for all target products into hAChE were performed and confirmed strong binding to the enzyme. These results provide a promising and new starting point to improve acetylcholinesterase inhibitors and explore novel treatment options against Alzheimer’s disease.

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

Synthetic and semi-synthetic drugs as promising therapeutic option for the treatment of COVID-19

2020 ◽  
Vol 20 ◽  
Author(s):  
Ekta Shirbhate ◽  
Preeti Patel ◽  
Vijay K Patel ◽  
Ravichandran Veerasamy ◽  
Prabodh C Sharma ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Antiviral Treatment ◽  
The Novel ◽  
Clinical Experiences ◽  
Synthetic Compounds ◽  
Synthetic Drugs ◽  
Global Pandemic ◽  
The World ◽  
Novel Coronavirus

: The novel coronavirus disease-19 (COVID-19), a global pandemic that emerged from Wuhan, China has today travelled all around the world, so far 216 countries or territories with 21,732,472 people infected and 770,866 deaths globally (as per WHO COVID-19 update dated August 18, 2020). Continuous efforts are being made to repurpose the existing drugs and develop vaccines for combating this infection. Despite, to date, no certified antiviral treatment or vaccine prevails. Although, few candidates have displayed their efficacy in in vitro studies and are being repurposed for COVID-19 treatment. This article summarizes synthetic and semi-synthetic compounds displaying potent activity in their clinical experiences or studies against COVID-19 and also focuses on mode of action of drugs being repositioned against COVID-19.

MiR-485-5p Promotes Neuron Survival through Mediating Rac1/Notch2 Signaling Pathway after Cerebral Ischemia/Reperfusion

2020 ◽  
Vol 17 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Xuan Chen ◽  
Sumei Zhang ◽  
Peipei Shi ◽  
Yangli Su ◽  
Dong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Small Gtpase ◽  
Luciferase Reporter ◽  
Pathological Feature ◽  
In Cells

Objective: Ischemia-reperfusion (I/R) injury is a pathological feature of ischemic stroke. This study investigated the regulatory role of miR-485-5p in I/R injury. Methods: SH-SY5Y cells were induced with oxygen and glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Cells were transfected with designated constructs (miR-485- 5p mimics, miR-485-5p inhibitor, lentiviral vectors overexpressing Rac1 or their corresponding controls). Cell viability was evaluated using the MTT assay. The concentrations of lactate dehydrogenase, malondialdehyde, and reactive oxygen species were detected to indicate the degree of oxidative stress. Flow cytometry and caspase-3 activity assay were used for apoptosis assessment. Dual-luciferase reporter assay was performed to confirm that Rac family small GTPase 1 (Rac1) was a downstream gene of miR-485-5p. Results: OGD/R resulted in decreased cell viability, elevated oxidative stress, increased apoptosis, and downregulated miR-485-5p expression in SH-SY5Y cells. MiR-485-5p upregulation alleviated I/R injury, evidenced by improved cell viability, decreased oxidative markers, and reduced apoptotic rate. OGD/R increased the levels of Rac1 and neurogenic locus notch homolog protein 2 (Notch2) signaling-related proteins in cells with normal miR-485-5p expression, whereas miR- 485-5p overexpression successfully suppressed OGD/R-induced upregulation of these proteins. Furthermore, the delivery of vectors overexpressing Rac1 in miR-485-5p mimics-transfected cells reversed the protective effect of miR-485-5p in cells with OGD/R-induced injury. Conclusion: This study showed that miR-485-5p protected cells following I/R injury via targeting Rac1/Notch2 signaling suggest that targeted upregulation of miR-485-5p might be a promising therapeutic option for the protection against I/R injury.

Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

2019 ◽  
Vol 16 (10) ◽  
pp. 837-845
Author(s):  
Sandhya Jonnala ◽  
Bhaskar Nameta ◽  
Murthy Chavali ◽  
Rajashaker Bantu ◽  
Pallavi Choudante ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Mouse Skin ◽  
Coupling Reaction ◽  
Binding Mode ◽  
Biological Evaluation ◽  
Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

Sign in / Sign up

Export Citation Format

Share Document