Clove Constituents as new leads for the Design and development of Multi-targeted Anti-Alzheimer activity

2021 ◽  
pp. 3515-3522
Author(s):  
Safiya Sultana T ◽  
Sivakumar M
Keyword(s):  
Virtual Screening ◽  
Oleanolic Acid ◽  
Docking Simulation ◽  
In Vitro Assays ◽  
Syzygium Aromaticum ◽  
Potential Candidate ◽  
Multiple Targets ◽  
Target Action ◽  
Anti Oxidant ◽  
Toxicity Estimation

Objective: To use virtual screening analysis to screen out the phytoconstituents of Syzygium aromaticum against multiple targets of AD and determine its anti-oxidant and inflammatory inhibitory property. Methods: The compounds listed out from Syzygium aromaticum were subjected to virtual screening based on their drug likeness property and bioactivity scores. The molecular docking simulation such as HEX 8.0, PyRx, MVD along with Auto Dock 4.2 were employed to determine the potential candidate for providing activity against multiple targets of AD. The toxicity estimation was also carried out using TEST software. The potential candidate was further evaluated using DPPH, FRAT, Albumin denaturation and Proteinase inhibition method. Results: Only eight phytoconstituents were selected for virtual screening as they possessed drug likeness property and better bioactivity score for inhibition of kinases, proteases and enzymes. The docking results from various tools predicted that Oleanolic acid can be considered as potential constituents for multi-target action against AD. Toxicity estimation was in range. It also exhibited anti-oxidant and inflammatory inhibition providing its evidence for anti-AD activity. Conclusion: Taken together, these virtual screening results and in-vitro assays suggest that Oleanolic acid has multi target action against AD, which can be proved further with in-vivo studies.

scholarly journals Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4424
Author(s):  
Uzma Arshad ◽  
Sibtain Ahmed ◽  
Nusrat Shafiq ◽  
Zaheer Ahmad ◽  
Aqsa Hassan ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Catalytic Amount ◽  
Pyrimidine Derivatives ◽  
Qsar Studies ◽  
Lead Compounds ◽  
Biological Potential ◽  
Anti Cancer ◽  
Anti Oxidant ◽  
Vitro Analysis

Objective: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. Methodology: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. Results: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.

scholarly journals Pharmacologic Activities¬ of 3’-Hydroxypterostilbene: Cytotoxic, Anti-Oxidant, Anti-Adipogenic, Anti-Inflammatory, Histone Deacetylase and Sirtuin 1 Inhibitory Activity

2015 ◽  
Vol 18 (4) ◽  
pp. 713 ◽  
Author(s):  
Jody K Takemoto ◽  
Connie M. Remsberg ◽  
Neal M. Davies
Keyword(s):  
Histone Deacetylase ◽  
Inhibitory Activity ◽  
Sirtuin 1 ◽  
In Vitro Assays ◽  
Naturally Occurring ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
First Time ◽  
Stilbene Compounds

Purpose: Delineate the selected pharmacodynamics of a naturally occurring stilbene 3’-Hydroxypterostilbene. Objective: Characterize for the first time the pharmacodynamics bioactivity in several in-vitro assays with relevant roles in heart disease, inflammation, cancer, and diabetes etiology and pathophysiology. Methods: 3’-Hydroxypterostilbene was studied in in-vitro assays to identify possible bioactivity. Results: 3’-Hydroxypterostilbene demonstrated anti-oxidant, anti-inflammatory, cytotoxic, anti-adipogenic, histone deacetylase, and sirtuin-1 inhibitory activity. Conclusions: The importance of understanding individual stilbene pharmacologic activities were delineated.  Small changes in chemical structure of stilbene compounds result in significant pharmacodynamic differences. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals In SilicoInvestigation of Potential Pyruvate Kinase M2 Regulators from Traditional Chinese Medicine against Cancers

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Kuen-Bao Chen ◽  
Hsin-Yi Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Virtual Screening ◽  
Drug Development ◽  
Pyruvate Kinase ◽  
Md Simulation ◽  
Docking Simulation ◽  
Target Protein ◽  
Binding Affinities ◽  
Pyruvate Kinase M2 ◽  
Lead Compounds ◽  
The Stability

A recent research in cancer research demonstrates that tumor-specific pyruvate kinase M2 (PKM2) plays an important role in chromosome segregation and mitosis progression of tumor cells. To improve the drug development of TCM compounds, we aim to identify potent TCM compounds as lead compounds of PKM2 regulators. PONDR-Fit protocol was utilized to predict the disordered disposition in the binding domain of PKM2 protein before virtual screening as the disordered structure in the protein may cause the side effect and downregulation of the possibility of ligand to bind with target protein. MD simulation was performed to validate the stability of interactions between PKM2 proteins and each ligand after virtual screening. The top TCM compounds, saussureamine C and precatorine, extracted fromLycium chinenseMill. andAbrus precatoriusL., respectively, have higher binding affinities with target protein in docking simulation than control. They have stable H-bonds with residues A:Lys311 and some other residues in both chains of PKM2 protein. Hence, we propose the TCM compounds, saussureamine C and precatorine, as potential candidates as lead compounds for further study in drug development process with the PKM2 protein against cancer.

scholarly journals Low dose amiodarone reduces tumor growth and angiogenesis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eliana Steinberg ◽  
Arnon Fluksman ◽  
Chalom Zemmour ◽  
Katerina Tischenko ◽  
Adi Karsch-Bluman ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Low Dose ◽  
Tumor Model ◽  
In Vitro Assays ◽  
Potential Candidate ◽  
Key Factor ◽  
Angiogenic Effect

Abstract Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug’s harmful side effects.

scholarly journals Eugenol prevents fMLF-induced superoxide anion production in human neutrophils by inhibiting ERK1/2 signaling pathway and p47phox phosphorylation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amina Chniguir ◽  
Coralie Pintard ◽  
Dan Liu ◽  
Pham My-Chan Dang ◽  
Jamel El-Benna ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Human Neutrophils ◽  
Syzygium Aromaticum ◽  
Superoxide Anion Production ◽  
Anion Production ◽  
Reduction Assay ◽  
Cytochrome C Reduction ◽  
Phenolic Group ◽  
Anti Oxidant ◽  
Neutrophil Superoxide

AbstractEugenol is a polyphenol extracted from Syzygium aromaticum essential oil. It is known to have anti-inflammatory and chemoprotective properties as well as a potent anti-oxidant activity due the presence of its phenolic group. In this study, we examined the effects of eugenol on neutrophil superoxide production, a key process involved in innate immunity and inflammation. Superoxide anion generationin human neutrophils was measured by cytochrome c reduction assay. Western blotting was used to analyze the phosphorylation of, p47phox, MAPKinases (p38 and ERK1/2), MEK1/2 and Raf, key proteins involved in the activation of NADPH oxidase. Pretreatment of neutrophils by increasing concentrations (2.5 µg/mL–20 µg/mL) of eugenol for 30 min, inhibited significantly (p < 0.001) superoxide anion generation induced by the chemotactic peptide formyl-Met-Leu-Phe (fMLF) with an IC50 of 5 µg/mL. Phorbolmyristate acetate (PMA)-stimulated O2− production was affected only at the highest eugenol concentration (20 µg/mL). Results showed that eugenol decreased the phosphorylation of p47phox onSer-345 and Ser-328, the translocation of p47phox to the membranesand the phosphorylation of Raf, MEK1/2 and ERK1/2 proteins. Taken together, our results suggest that eugenol inhibits the generation of superoxide anion by neutrophils via the inhibition of Raf/MEK/ERK1/2/p47phox-phosphorylation pathway.

scholarly journals Semisynthesis of Derivatives of Oleanolic Acid fromSyzygium aromaticumand Their Antinociceptive and Anti-Inflammatory Properties

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Sibusiso Rali ◽  
Opeoluwa O. Oyedeji ◽  
Olukayode O. Aremu ◽  
Adebola O. Oyedeji ◽  
Benedicta N. Nkeh-Chungag
Keyword(s):  
Oleanolic Acid ◽  
Acetyl Derivative ◽  
Syzygium Aromaticum ◽  
Analgesic Effects ◽  
Pentacyclic Triterpenoid ◽  
Ft Ir ◽  
Anti Inflammatory ◽  
Pain Test ◽  
Layer Chromatography ◽  
Derivatives Of

Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract ofSyzygium aromaticumflower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties.

Virtual Screening in Chinese Herbs with Multi-Target Effect on Alzheimer's Disease

2013 ◽  
Vol 765-767 ◽  
pp. 256-260
Author(s):  
Yan Ling Zhang ◽  
Yuan Ming Wang ◽  
Yan Jiang Qiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Virtual Screening ◽  
Glycogen Synthase ◽  
Chinese Herbs ◽  
Multiple Targets ◽  
Active Compounds ◽  
Ache Inhibitors ◽  
Gsk 3Β ◽  
Pharmacophore Models

Multiple targets which closely related to Alzheimer's disease (AD) pathogenesis were selected for pharmacophore models generation and virtual screening in Chinese herbs. The targets comprised Acetylcholinesterase (AchE), muscarinic receptor 1 (M1), γ-secretase and glycogen synthase kinase 3β (GSK-3β). The pharmacophore models, which of AchE inhibitors, M1 agonists, γ-secretase inhibitors and GSK-3β inhibitors, were constructed by distance comparison method. Four testing databases for the evaluation of pharmacophore models were constructed with the active compounds with clearly marked activity on each target. The metric CAI (Comprehensive Appraisal Index) was then used to evaluate and obtain the best pharmacophore models of each target, which were then applied to screen the Traditional Chinese Medicine Database for potential active compounds in Chinese herbs. Four common used herbs were obtained, which contain the active compounds and can act on multiple targets, and were expected to have multiple activity of anti-AD disease.

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