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Article ; Online: Regulation of tumor metabolism by post translational modifications on metabolic enzymes.

Sawant Dessai, Abhisha / Kalhotra, Poonam / Novickis, Aaron T / Dasgupta, Subhamoy

2022 Volume 30, Issue 4, Page(s) 548–558

Abstract: Metabolic reprogramming is a hallmark of cancer development, progression, and metastasis. Several metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, lipid metabolism, and glutamine catabolism are frequently altered to support cancer ... ...

Abstract	Metabolic reprogramming is a hallmark of cancer development, progression, and metastasis. Several metabolic pathways such as glycolysis, tricarboxylic acid (TCA) cycle, lipid metabolism, and glutamine catabolism are frequently altered to support cancer growth. Importantly, the activity of the rate-limiting metabolic enzymes in these pathways are specifically modulated in cancer cells. This is achieved by transcriptional, translational, and post translational regulations that enhance the expression, activity, stability, and substrate sensitivity of the rate-limiting enzymes. These mechanisms allow the enzymes to retain increased activity supporting the metabolic needs of rapidly growing tumors, sustain their survival in the hostile tumor microenvironments and in the metastatic lesions. In this review, we primarily focused on the post translational modifications of the rate-limiting enzymes in the glucose and glutamine metabolism, TCA cycle, and fatty acid metabolism promoting tumor progression and metastasis.
MeSH term(s)	Humans ; Glutamine/metabolism ; Neoplasms/pathology ; Glycolysis ; Citric Acid Cycle ; Protein Processing, Post-Translational ; Tumor Microenvironment
Chemical Substances	Glutamine (0RH81L854J)
Language	English
Publishing date	2022-08-23
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1212513-1
ISSN	1476-5500 ; 0929-1903
ISSN (online)	1476-5500
ISSN	0929-1903
DOI	10.1038/s41417-022-00521-x
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Article ; Online: Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors.

Kalhotra, Poonam / Chittepu, Veera C S R / Osorio-Revilla, Guillermo / Gallardo-Velazquez, Tzayhri

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 4

Abstract: Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that ... ...

Abstract	Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that has been shown to reduce virus replication, and its high-resolution 3D structures in complex with inhibitors have been solved. Previously, we had demonstrated the potential of natural compounds such as serine protease inhibitors eventually leading us to hypothesize that FDA-approved marine drugs have the potential to inhibit the biological activity of SARS-CoV-2 main protease. Initially, field-template and structure-activity atlas models were constructed to understand and explain the molecular features responsible for SARS-CoVID-2 main protease inhibitors, which revealed that Eribulin Mesylate, Plitidepsin, and Trabectedin possess similar characteristics related to SARS-CoVID-2 main protease inhibitors. Later, protein-ligand interactions are studied using ensemble molecular-docking simulations that revealed that marine drugs bind at the active site of the main protease. The three-dimensional reference interaction site model (3D-RISM) studies show that marine drugs displace water molecules at the active site, and interactions observed are favorable. These computational studies eventually paved an interest in further in vitro studies. Finally, these findings are new and indeed provide insights into the role of FDA-approved marine drugs, which are already in clinical use for cancer treatment as a potential alternative to prevent and treat infected people with SARS-CoV-2.
MeSH term(s)	Catalytic Domain ; Depsipeptides/chemistry ; Depsipeptides/pharmacology ; Drug Repositioning ; Furans/chemistry ; Furans/pharmacology ; Humans ; Ketones/chemistry ; Ketones/pharmacology ; Models, Molecular ; Molecular Docking Simulation ; Peptide Hydrolases/chemistry ; Peptide Hydrolases/metabolism ; Quantitative Structure-Activity Relationship ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Serine Proteinase Inhibitors/chemistry ; Serine Proteinase Inhibitors/pharmacology ; Trabectedin/chemistry ; Trabectedin/pharmacology ; Viral Proteins/antagonists & inhibitors ; Virus Replication/drug effects
Chemical Substances	Depsipeptides ; Furans ; Ketones ; Serine Proteinase Inhibitors ; Viral Proteins ; Peptide Hydrolases (EC 3.4.-) ; Trabectedin (ID0YZQ2TCP) ; eribulin (LR24G6354G) ; plitidepsin (Y76ID234HW)
Language	English
Publishing date	2021-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26040936
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Article ; Online: Field-Template, QSAR, Ensemble Molecular Docking, and 3D-RISM Solvation Studies Expose Potential of FDA-Approved Marine Drugs as SARS-CoVID-2 Main Protease Inhibitors

Poonam Kalhotra / Veera C. S. R. Chittepu / Guillermo Osorio-Revilla / Tzayhri Gallardo-Velazquez

Molecules, Vol 26, Iss 4, p

2021 Volume 936

Abstract	Currently, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected people among all countries and is a pandemic as declared by the World Health Organization (WHO). SARS-CoVID-2 main protease is one of the therapeutic drug targets that has been shown to reduce virus replication, and its high-resolution 3D structures in complex with inhibitors have been solved. Previously, we had demonstrated the potential of natural compounds such as serine protease inhibitors eventually leading us to hypothesize that FDA-approved marine drugs have the potential to inhibit the biological activity of SARS-CoV-2 main protease. Initially, field-template and structure–activity atlas models were constructed to understand and explain the molecular features responsible for SARS-CoVID-2 main protease inhibitors, which revealed that Eribulin Mesylate, Plitidepsin, and Trabectedin possess similar characteristics related to SARS-CoVID-2 main protease inhibitors. Later, protein–ligand interactions are studied using ensemble molecular-docking simulations that revealed that marine drugs bind at the active site of the main protease. The three-dimensional reference interaction site model (3D-RISM) studies show that marine drugs displace water molecules at the active site, and interactions observed are favorable. These computational studies eventually paved an interest in further in vitro studies. Finally, these findings are new and indeed provide insights into the role of FDA-approved marine drugs, which are already in clinical use for cancer treatment as a potential alternative to prevent and treat infected people with SARS-CoV-2.
Keywords	SARS-CoV-2 ; CoVID-2 main protease ; FDA-approved marine drugs ; ensemble molecular docking ; field-template models ; antivirals ; Organic chemistry ; QD241-441
Subject code	540
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phytochemicals in Garlic Extract Inhibit Therapeutic Enzyme DPP-4 and Induce Skeletal Muscle Cell Proliferation: A Possible Mechanism of Action to Benefit the Treatment of Diabetes Mellitus.

Kalhotra, Poonam / Chittepu, Veera C S R / Osorio-Revilla, Guillermo / Gallardo-Velazquez, Tzayhri

Biomolecules

2020 Volume 10, Issue 2

Abstract: Diabetes mellitus is a severe health problem in Mexico, and its prevalence is increasing exponentially every year. Recently, DPP-4 (dipeptidyl peptidase-4) inhibitors have become attractive oral anti-hyperglycemic agents to reduce the pathology of ... ...

Abstract	Diabetes mellitus is a severe health problem in Mexico, and its prevalence is increasing exponentially every year. Recently, DPP-4 (dipeptidyl peptidase-4) inhibitors have become attractive oral anti-hyperglycemic agents to reduce the pathology of diabetes. Gliptin's family, such as sitagliptin, vildagliptin, and alogliptin, are in clinical use to treat diabetes mellitus but possess side effects. Therefore, there is a specific need to look for new therapeutic scaffolds (biomolecules). Garlic bulb is widely used as a traditional remedy for the treatment of diabetes. The garlic extracts are scientifically proven to control glucose levels in patients with diabetes, despite the unknown mechanism of action. The aim of the study is to investigate the antidiabetic effects of ultrasonication assisted garlic bulb extract. To achieve this, in-vitro assays such as DPP-4 inhibitory and antioxidant activities were investigated. Further, functional group analysis using FTIR and identification of phytochemicals using mass spectrometry analysis was performed. The results showed that 70.9 µg/mL of garlic bulb extract inhibited 50% DPP-4 activity. On top of that, the garlic extract exhibited a 20% scavenging activity, equivalent to 10 µg/mL of ascorbic acid. Molecular docking simulations on identified phytochemicals using mass spectrometry revealed their potential binding at the DPP-4 druggable region, and therefore the possible DPP-4 inhibition mechanism. These results suggest that prepared garlic extract contains phytochemicals that inhibit DPP-4 and have antioxidant activity. Also, the prepared extract induces skeletal muscle cell proliferation that demonstrates the antidiabetic effect and its possible mechanism of action.
MeSH term(s)	Animals ; Antioxidants/therapeutic use ; Cell Culture Techniques ; Cell Proliferation/drug effects ; Diabetes Mellitus, Type 2/drug therapy ; Dipeptidyl Peptidase 4/chemistry ; Dipeptidyl Peptidase 4/metabolism ; Dipeptidyl Peptidase 4/therapeutic use ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Garlic/metabolism ; Hypoglycemic Agents/pharmacology ; Mexico ; Molecular Docking Simulation ; Muscle, Skeletal/drug effects ; Phytochemicals/therapeutic use ; Plant Extracts/pharmacology ; Rats
Chemical Substances	Antioxidants ; Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemic Agents ; Phytochemicals ; Plant Extracts ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
Language	English
Publishing date	2020-02-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom10020305
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Article: Chrysin in Combination with Insulin Promotes Glucose Uptake in Skeletal Muscle Cell: Impact of Combination Therapy in Diabetes Myopathy (P01-031-19)

Kalhotra, Poonam / Chittepu, Veera Chandra Sekhar Reddy / Gallardo-Velazquez, Tzayhri / Osorio-Revilla, Guillermo

Current developments in nutrition. 2019 June 13, v. 3, no. Supplement_1

2019

Abstract: The objective of the current study was examining the beneficial effects of DPP4 inhibitor chrysin alone and in combination with insulin benefits diabetes myopathy. Sulforhodamine B (SRB) protein-dye was used to determine the acute toxicity, and 1H NMR ... ...

Abstract	The objective of the current study was examining the beneficial effects of DPP4 inhibitor chrysin alone and in combination with insulin benefits diabetes myopathy. Sulforhodamine B (SRB) protein-dye was used to determine the acute toxicity, and 1H NMR spectroscopy was used to identify and quantify glucose levels to assess glucose uptake on treatments chrysin and combination of chrysin with Insulin on differentiated skeletal muscle cells. Pathway analysis was carried out using omics net web server. All experiments were conducted in triplicates, and all data in the graph represent Mean ± S.D. Graph pad software was used to calculate One-way analysis of variance (ANOVA), computed p-value among different groups and values with P < 0.05 is significant. Results showed that 250 μM chrysin and combination (10 nM Insulin with 250 μM chrysin) treatments are not acutely toxic to skeletal muscle cells and proliferates the cells significant to insulin-treated skeletal muscle cells (Figure 1A). Glucose metabolite levels are studied as skeletal muscle cells adopted cell proliferative and to demonstrate our hypothesis on glucose metabolism. Significant differences were observed in skeletal muscle cells treated with insulin, chrysin, and combination (Figure 1B). It is observed that chrysin alone, combination increases glucose uptake significantly in comparison to control cells. Pathway analysis revealed that GPCR signaling and immune-related signaling plays a role in proliferating skeletal muscle cells to regulate glucose metabolism. The results of this study propose the use of natural compound chrysin in combination with insulin to promote skeletal muscle health in diabetes mellitus. The combination identified herein must be considered for future therapies to control diabetic myopathy in preclinical and clinical studies. Chrysin can also be applied as a supplement in the diet as well, to control diabetic myopathy. Authors wish to express their gratitude to Escuela Nacional de Ciencias Biológicas-Instituto Politécnico Nacional (ENCB-IPN) for providing financial support for the present study.
Keywords	acute toxicity ; analysis of variance ; chrysin ; clinical trials ; computer software ; diabetes mellitus ; diet ; glucose ; G-protein coupled receptors ; insulin ; Internet ; metabolism ; metabolites ; muscular diseases ; myocytes ; nuclear magnetic resonance spectroscopy ; skeletal muscle ; therapeutics
Language	English
Dates of publication	2019-0613
Publishing place	Oxford University Press
Document type	Article
ISSN	2475-2991
DOI	10.1093/cdn/nzz028.P01-031-19
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Discovery of Galangin as a Potential DPP-4 Inhibitor That Improves Insulin-Stimulated Skeletal Muscle Glucose Uptake: A Combinational Therapy for Diabetes.

Kalhotra, Poonam / Chittepu, Veera C S R / Osorio-Revilla, Guillermo / Gallardo-Velázquez, Tzayhri

International journal of molecular sciences

2019 Volume 20, Issue 5

Abstract: Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and ... ...

Abstract	Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of -24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the proliferation of rat L6 skeletal muscle cells. The combination of galangin with insulin benefits regulation of glucose levels significantly in comparison to galangin alone (
MeSH term(s)	Animals ; Cell Proliferation/drug effects ; Diabetes Mellitus, Type 2 ; Dipeptidyl-Peptidase IV Inhibitors/chemistry ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Flavonoids/chemistry ; Flavonoids/pharmacology ; Glucose/metabolism ; Insulin/metabolism ; Models, Molecular ; Molecular Conformation ; Muscle, Skeletal/metabolism ; Protein Binding ; Rats ; Reproducibility of Results ; Structure-Activity Relationship
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; Flavonoids ; Insulin ; galangin (142FWE6ECS) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2019-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20051228
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Article ; Online: Structure⁻Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor: An Integrated In Silico and In Vitro Study.

Kalhotra, Poonam / Chittepu, Veera C S R / Osorio-Revilla, Guillermo / Gallardo-Velázquez, Tzayhri

Molecules (Basel, Switzerland)

2018 Volume 23, Issue 6

Abstract: Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and ... ...

Abstract	Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer. This study describes the development of field template, field-based qualitative structure⁻activity relationship (SAR) model demonstrating DPP-4 inhibitors of natural origin, and the same model is used to screen virtually focused food database composed of polyphenols as potential DPP-4 inhibitors. Compounds’ similarity to field template, and novelty score “high and very high”, were used as primary criteria to identify novel DPP-4 inhibitors. Molecular docking simulations were performed on the resulting natural compounds using FlexX algorithm. Finally, one natural compound, chrysin, was chosen to be evaluated experimentally to demonstrate the applicability of constructed SAR model. This study provides the molecular insights necessary in the discovery of new leads as DPP-4 inhibitors, to improve the potency of existing DPP-4 natural inhibitors.
MeSH term(s)	Algorithms ; Animals ; Computer Simulation ; Dipeptidyl-Peptidase IV Inhibitors/chemistry ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Flavonoids/chemistry ; Flavonoids/pharmacology ; Humans ; In Vitro Techniques ; Molecular Docking Simulation ; Rats ; Structure-Activity Relationship
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; Flavonoids ; chrysin (3CN01F5ZJ5)
Language	English
Publishing date	2018-06-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules23061368
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Article ; Online: Discovery of Galangin as a Potential DPP-4 Inhibitor That Improves Insulin-Stimulated Skeletal Muscle Glucose Uptake

Poonam Kalhotra / Veera C. S. R. Chittepu / Guillermo Osorio-Revilla / Tzayhri Gallardo-Velázquez

International Journal of Molecular Sciences, Vol 20, Iss 5, p

A Combinational Therapy for Diabetes

2019 Volume 1228

Abstract	Dipeptidyl peptidase-4 (DPP-4) is a well-known therapeutic drug target proven to reduce blood glucose levels in diabetes mellitus, and clinically, DPP-4 inhibitors are used in combination with other anti-diabetic agents. However, side effects and skeletal muscle health are not considered in the treatment for diabetic patients. Recently, natural compounds have been proven to inhibit DPP-4 with fewer side effects. In this work, initially, molecular docking simulations revealed that a natural compound, Galangin, possess a binding energy of −24 KJ/mol and interaction residues SER 630 and TYR 547, that are responsible for potent DPP-4 inhibition. In vitro studies showed that galangin not only inhibits DPP-4 in a concentration-dependent manner but also regulates glucose levels, enabling the proliferation of rat L6 skeletal muscle cells. The combination of galangin with insulin benefits regulation of glucose levels significantly in comparison to galangin alone (p < 0.05). These findings suggest the beneficial effect of the use of galangin, both alone or in combination with insulin, to reduce glucose levels and improve skeletal muscle health in diabetes mellitus.
Keywords	diabetes mellitus ; molecular docking ; galangin ; DPP-4 inhibitor ; combination therapy ; skeletal muscle cell health ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Repurposing of FDA-Approved NSAIDs for DPP-4 Inhibition as an Alternative for Diabetes Mellitus Treatment: Computational and in Vitro Study.

Chittepu, Veera C S R / Kalhotra, Poonam / Osorio-Gallardo, Tzayhri / Gallardo-Velázquez, Tzayhri / Osorio-Revilla, Guillermo

Pharmaceutics

2019 Volume 11, Issue 5

Abstract: A drug repurposing strategy could be a potential approach to overcoming the economic costs for diabetes mellitus (DM) treatment incurred by most countries. DM has emerged as a global epidemic, and an increase in the outbreak has led developing countries ... ...

Abstract	A drug repurposing strategy could be a potential approach to overcoming the economic costs for diabetes mellitus (DM) treatment incurred by most countries. DM has emerged as a global epidemic, and an increase in the outbreak has led developing countries like Mexico, India, and China to recommend a prevention method as an alternative proposed by their respective healthcare sectors. Incretin-based therapy has been successful in treating diabetes mellitus, and inhibitors like sitagliptin, vildagliptin, saxagliptin, and alogliptin belong to this category. As of now, drug repurposing strategies have not been used to identify existing therapeutics that can become dipeptidyl peptidase-4 (DPP-4) inhibitors. Hence, this work presents the use of bioinformatics tools like the Activity Atlas model, flexible molecular docking simulations, and three-dimensional reference interaction site model (3D-RISM) calculations to assist in repurposing Food and Drug Administration (FDA)-approved drugs into specific nonsteroidal anti-inflammatory medications such as DPP-4 inhibitors. Initially, the Activity Atlas model was constructed based on the top scoring DPP-4 inhibitors, and then the model was used to understand features of nonsteroidal anti-inflammatory drugs (NSAIDs) as a function of electrostatic, hydrophobic, and active shape features of DPP-4 inhibition. The FlexX algorithm was used to infer protein-ligand interacting residues, and binding energy, to predict potential draggability towards the DPP-4 mechanism of action. 3D-RISM calculations on piroxicam-bound DPP-4 were used to understand the stability of water molecules at the active site. Finally, piroxicam was chosen as the repurposing drug to become a new DPP-4 inhibitor and validated experimentally using fluorescence spectroscopy assay. These findings are novel and provide new insights into the role of piroxicam as a new lead to inhibit DPP-4 and, taking into consideration the biological half-life of piroxicam, it can be proposed as a possible therapeutic strategy for treating diabetes mellitus.
Language	English
Publishing date	2019-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics11050238
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Article ; Online: Structure–Activity Relationship and Molecular Docking of Natural Product Library Reveal Chrysin as a Novel Dipeptidyl Peptidase-4 (DPP-4) Inhibitor

Poonam Kalhotra / Veera C. S. R. Chittepu / Guillermo Osorio-Revilla / Tzayhri Gallardo-Velázquez

Molecules, Vol 23, Iss 6, p

An Integrated In Silico and In Vitro Study

2018 Volume 1368

Abstract	Numerous studies indicate that diets with a variety of fruits and vegetables decrease the incidence of severe diseases, like diabetes, obesity, and cancer. Diets contain a variety of bioactive compounds, and their features, like diverge scaffolds, and structural complexity make them the most successful source of potential leads or hits in the process of drug discovery and drug development. Recently, novel serine protease dipeptidyl peptidase-4 (DPP-4) inhibitors played a role in the management of diabetes, obesity, and cancer. This study describes the development of field template, field-based qualitative structure–activity relationship (SAR) model demonstrating DPP-4 inhibitors of natural origin, and the same model is used to screen virtually focused food database composed of polyphenols as potential DPP-4 inhibitors. Compounds’ similarity to field template, and novelty score “high and very high”, were used as primary criteria to identify novel DPP-4 inhibitors. Molecular docking simulations were performed on the resulting natural compounds using FlexX algorithm. Finally, one natural compound, chrysin, was chosen to be evaluated experimentally to demonstrate the applicability of constructed SAR model. This study provides the molecular insights necessary in the discovery of new leads as DPP-4 inhibitors, to improve the potency of existing DPP-4 natural inhibitors.
Keywords	natural products ; field-based virtual screening ; structure–activity relationship model ; molecular docking ; dipeptidyl peptidase-4 enzyme ; Organic chemistry ; QD241-441
Subject code	540
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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