In vitro Acetylcholinesterase inhibitory activity of polyphenolic compounds identified from Matricaria recutita

2020 ◽  
Vol 19 (08) ◽  
pp. 2050029
Author(s):  
Suhailah Wasman Qader ◽  
Hassan H. Abdallah ◽  
Mstaffa Zahid ◽  
Lee Suan Chua
Keyword(s):  
Inhibitory Activity ◽  
Ultra Performance Liquid Chromatography ◽  
Docking Studies ◽  
Cognitive Disorder ◽  
Polyphenolic Compounds ◽  
Accurate Analysis ◽  
Matricaria Recutita ◽  
Key Enzyme

Acetylcholinesterase (AChE) is a key enzyme enhancing the cognitive disorder, leading to Alzheimer’s disease, and AChE inhibition is a crucial therapeutic mechanism against it. Matricaria recutita (MR) is widely used as a herbal medicine due to its phytotherapeutic properties. For this reason, MR flower was evaluated to identify polyphenolic compounds (PC), and then each PC is examined for AChE inhibitory activity. The ultra-performance liquid chromatography-electrospray tandem mass spectrometry UPLC-ESI-MS/MS was used to detect PC, and molecular docking was performed to insight potential inhibitory activity of PC against AChE. A series of 13 PC compounds were identified in the fractions of MR plant. Docking studies revealed that the inhibitory free energy and the position of the docked compounds in the active site are favored for the active compounds complex formed between AChE and the identified PC compounds. The accurate analysis of the docking result demonstrates that Kaempferol-3-O-rutinoside (KR) and Luteolin-8-C-glucoside (orientin) (LG) are the most significant inhibitory compounds against AChE. It can be concluded that MR is a significant source of PC compounds, and KR and LG are the most promising compounds that have high-affinity binding to AChE, based on docking outcome. Further experiments are recommended to explore in vivo enzyme compound interaction and toxicity models to establish the maximum suggested dose.

scholarly journals An In Silico and an In Vitro Inhibition Analysis of Glycogen Phosphorylase by Flavonoids, Styrylchromones, and Pyrazoles

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 306
Author(s):  
Sónia Rocha ◽  
Natália Aniceto ◽  
Rita C. Guedes ◽  
Hélio M. T. Albuquerque ◽  
Vera L. M. Silva ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Glycogen Phosphorylase ◽  
Inhibitory Effect ◽  
Docking Studies ◽  
Potent Inhibitory Effect ◽  
Key Enzyme ◽  
Experimental Findings

Glycogen phosphorylase (GP) is a key enzyme in the glycogenolysis pathway. GP inhibitors are currently under investigation as a new liver-targeted approach to managing type 2 diabetes mellitus (DM). The aim of the present study was to evaluate the inhibitory activity of a panel of 52 structurally related chromone derivatives; namely, flavonoids, 2-styrylchromones, 2-styrylchromone-related derivatives [2-(4-arylbuta-1,3-dien-1-yl)chromones], and 4- and 5-styrylpyrazoles against GP, using in silico and in vitro microanalysis screening systems. Several of the tested compounds showed a potent inhibitory effect. The structure–activity relationship study indicated that for 2-styrylchromones and 2-styrylchromone-related derivatives, the hydroxylations at the A and B rings, and in the flavonoid family, as well as the hydroxylation of the A ring, were determinants for the inhibitory activity. To support the in vitro experimental findings, molecular docking studies were performed, revealing clear hydrogen bonding patterns that favored the inhibitory effects of flavonoids, 2-styrylchromones, and 2-styrylchromone-related derivatives. Interestingly, the potency of the most active compounds increased almost four-fold when the concentration of glucose increased, presenting an IC50 < 10 µM. This effect may reduce the risk of hypoglycemia, a commonly reported side effect of antidiabetic agents. This work contributes with important considerations and provides a better understanding of potential scaffolds for the study of novel GP inhibitors.

Design, synthesis and biological evaluation of 3-(2-(benzo[d]thiazol-2- ylthio)acetamido)benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B

2020 ◽  
Vol 17 ◽  
Author(s):  
Monika Rakse ◽  
Chandrabose Karthikeyan ◽  
Narayana Subbiah Hari Narayana Moorthy ◽  
Ram Kishore Agrawal
Keyword(s):  
Benzoic Acid ◽  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Tyrosine Phosphatase ◽  
Docking Studies ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Benzoic Acid Derivatives

Background: Protein Tyrosine Phosphatase 1B (PTP1B) is an attractive target for antidiabetic drug discovery owing to its pivotal role as a negative regulator of insulin and leptin signaling. Objective: The objective of this research is to design, synthesize, and evaluate some acetamido benzoic acid derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors with therapeutic potential for Type II diabetes. Methods: 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)benzoic acid derivatives 4(a-j) were synthesized and characterized by employing spectral studies. All the synthesized compounds were screened for in vitro PTP1B inhibitory activity and the most potent compound in the series was also evaluated for in vivo anti-hyperglycemic activity using STZ induced diabetic Wistar rat model. Molecular docking studies were also performed with the most potent analog using FlexX docking algorithm to delineate its binding mode to the active site of the PTP1B. Results and Discussion: Among all the synthesized compounds, 3-(2-(benzo[d]thiazol-2-ylthio)acetamido)-4- methylbenzoic acid (4f) displayed good PTP1B inhibitory activity with an IC50 value of 11.17 μM. The compound also exhibited good anti-hyperglycemic efficacy in streptozotocin induced diabetic Wistar rats. Docking studies with 4f revealed the compound bound in the catalytic and second aryl binding site of the PTP1B. Conclusion: Overall, compound 4f with good in vitro PTP1B inhibitory potency and in vivo antihyperglycemic efficacy would be a valuable lead molecule for the development of acetamido benzoic acid based PTP1B inhibitors with antidiabetic potential.

Development and investigation of thiazolidinedione and pyrazoline compounds as antiangiogenic weapons targeting VEGFR-2

2021 ◽  
Author(s):  
Neha Upadhyay ◽  
Kalpana Tilekar ◽  
Sabreena Safuan ◽  
Alan P Kumar ◽  
Markus Schweipert ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Capillary Tube ◽  
Docking Studies ◽  
Tube Formation ◽  
Cellular Migration ◽  
Antiangiogenic Activity ◽  
Nanomolar Range

Background: Angiogenesis deregulation is often linked to cancer and is thus an essential target. Materials and methods: Twenty-nine compounds were developed as VEGFR-2 inhibitors. Compounds were evaluated to determine their antiangiogenic activity. Results: B1, PB11 and PB16 showed HUVEC's IC50 scores in the submicromolar range. B1, B2 and PB16 reduced cellular migration and capillary tube formation of HUVECs. VEGFR-2 inhibitory activity was found in the nanomolar range: 200 nM of B1, 500 nM of B2 and 600 nM of PB16. B1 and PB16 suppressed the formation of new capillaries on growing CAMs. B1 and PB16 occupied the ATP site and allosteric pocket of VEGFR-2 in docking studies. Conclusion: These compounds can target VEGFR-2 and are endowed with in vitro and in vivo antiangiogenic activity.

The Effects of Some Synthetic Compounds on In Vitro Fibrinolytic Activity Measured by Different Methods and the Relevance to Activity In Vivo

1972 ◽  
Vol 28 (03) ◽  
pp. 351-358
Author(s):  
A.J Baillie ◽  
A. K Sim
Keyword(s):  
Inhibitory Activity ◽  
Substrate Concentration ◽  
Fibrinolytic Activity ◽  
Synthetic Compounds ◽  
In Vitro Methods ◽  
Narrow Concentration Range

SummaryThe activity of several synthetic compounds, rated from good to poor (or inactive) fibrinolytic activators, has been assessed by two different commonly-used in vitro methods. Compounds shown to be active over a narrow concentration range in the hanging clot test were shown to be inhibitors of plasmin and trypsin in the casein-olytic test. The inhibitory activity of these compounds was shown to increase with increasing substrate concentration and apparent activity in the hanging clot test. Possible explanations and relevance of these observations are discussed.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

scholarly journals Novel Role for Albumin in Innate Immunity: Serum Albumin Inhibits the Growth of Blastomyces dermatitidis Yeast Form In Vitro

2003 ◽  
Vol 71 (11) ◽  
pp. 6648-6652 ◽  
Author(s):  
Steven Giles ◽  
Charles Czuprynski
Keyword(s):  
Molecular Weight ◽  
Inhibitory Activity ◽  
Mammalian Species ◽  
Blastomyces Dermatitidis ◽  
Low Molecular Weight ◽  
Rat Serum ◽  
Yeast Form ◽  
Domain Iii

ABSTRACT In this study we found that serum inhibitory activity against Blastomyces dermatitidis was principally mediated by albumin. This was confirmed in experiments using albumin from several mammalian species. Analbuminemic rat serum did not inhibit B. dermatitidis growth in vivo; however, the addition of albumin restored inhibitory activity. Inhibitory activity does not require albumin domain III and appears to involve binding of a low-molecular-weight yeast-derived growth factor.

scholarly journals Phytochemical Study and In Vitro Screening Focusing on the Anti-Aging Features of Various Plants of the Greek Flora

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1206
Author(s):  
Aimilia D. Sklirou ◽  
Maria T. Angelopoulou ◽  
Aikaterini Argyropoulou ◽  
Eliza Chaita ◽  
Vasiliki Ioanna Boka ◽  
...  
Keyword(s):  
Plant Species ◽  
High Performance ◽  
High Resolution Mass Spectrometry ◽  
Ultra Performance Liquid Chromatography ◽  
Skin Aging ◽  
Rosa Damascena ◽  
Phytochemical Study ◽  
Age Related

Skin health is heavily affected by ultraviolet irradiation from the sun. In addition, senile skin is characterized by major changes in the collagen, elastin and in the hyaluronan content. Natural products (NPs) have been shown to delay cellular senescence or in vivo aging by regulating age-related signaling pathways. Moreover, NPs are a preferable source of photoprotective agents and have been proven to be useful against the undesirable skin hyperpigmentation. Greek flora harvests great plant diversity with approximately 6000 plant species, as it has a wealth of NPs. Here, we report an extensive screening among hundreds of plant species. More than 440 plant species and subspecies were selected and evaluated. The extracts were screened for their antioxidant and anti-melanogenic properties, while the most promising were further subjected to various in vitro and cell-based assays related to skin aging. In parallel, their chemical profile was analyzed with High-Performance Thin-Layer Chromatography (HPTLC) and/or Ultra-Performance Liquid Chromatography High-Resolution Mass Spectrometry (UPLC-HRMS). A variety of extracts were identified that can be of great value for the cosmetic industry, since they combine antioxidant, photoprotective, anti-melanogenic and anti-aging properties. In particular, the methanolic extracts of Sideritis scardica and Rosa damascena could be worthy of further attention, since they showed interesting chemical profiles and promising properties against specific targets involved in skin aging.

scholarly journals USP29-mediated HIF1α stabilization is associated with Sorafenib resistance of hepatocellular carcinoma cells by upregulating glycolysis

Oncogenesis ◽  
2021 ◽  
Vol 10 (7) ◽  
Author(s):  
Ruize Gao ◽  
David Buechel ◽  
Ravi K. R. Kalathur ◽  
Marco F. Morini ◽  
Mairene Coto-Llerena ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcriptional Activity ◽  
Kinase Inhibitor ◽  
Aerobic Glycolysis ◽  
Hypoxia Inducible Factor ◽  
Aberrant Expression ◽  
Key Enzyme ◽  
Hcc Cells

AbstractUnderstanding the mechanisms underlying evasive resistance in cancer is an unmet medical need to improve the efficacy of current therapies. In hepatocellular carcinoma (HCC), aberrant expression of hypoxia-inducible factor 1 α (HIF1α) and increased aerobic glycolysis metabolism are drivers of resistance to therapy with the multi-kinase inhibitor Sorafenib. However, it has remained unknown how HIF1α is activated and how its activity and the subsequent induction of aerobic glycolysis promote Sorafenib resistance in HCC. Here, we report the ubiquitin-specific peptidase USP29 as a new regulator of HIF1α and of aerobic glycolysis during the development of Sorafenib resistance in HCC. In particular, we identified USP29 as a critical deubiquitylase (DUB) of HIF1α, which directly deubiquitylates and stabilizes HIF1α and, thus, promotes its transcriptional activity. Among the transcriptional targets of HIF1α is the gene encoding hexokinase 2 (HK2), a key enzyme of the glycolytic pathway. The absence of USP29, and thus of HIF1α transcriptional activity, reduces the levels of aerobic glycolysis and restores sensitivity to Sorafenib in Sorafenib-resistant HCC cells in vitro and in xenograft transplantation mouse models in vivo. Notably, the absence of USP29 and high HK2 expression levels correlate with the response of HCC patients to Sorafenib therapy. Together, the data demonstrate that, as a DUB of HIF1α, USP29 promotes Sorafenib resistance in HCC cells, in parts by upregulating glycolysis, thereby opening new avenues for therapeutically targeting Sorafenib-resistant HCC in patients.

scholarly journals Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110166
Author(s):  
Xin Yi Lim ◽  
Janice Sue Wen Chan ◽  
Terence Yew Chin Tan ◽  
Bee Ping Teh ◽  
Mohd Ridzuan Mohd Abd Razak ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Rna Binding ◽  
Symptomatic Relief ◽  
Andrographis Paniculata ◽  
Spike Protein ◽  
Rapid Review ◽  
In Silico Studies

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

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