In-silico identification of peroxisome proliferator-activated receptor (PPAR)α/γ agonists from Ligand Expo Components database

2020 ◽  
pp. 1-12
Author(s):  
Xiao-Yan Feng ◽  
Ting-Ting Ding ◽  
Ya-Ya Liu ◽  
Wei-Ren Xu ◽  
Xian-Chao Cheng
Keyword(s):  
In Silico ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
In Silico Identification

The Design and Evaluation of a Novel Monoamine Oxidase B Inhibitor Through in Silico Approach

2019 ◽  
Vol 10 (02) ◽  
Author(s):  
Hasanain Abdulhameed Odhar ◽  
Safaa Muhsen Kareem ◽  
Mohammed Ridha A Alhaideri ◽  
Mohammed Abbas Hasan ◽  
Werner J Geldenhuys
Keyword(s):  
Monoamine Oxidase ◽  
In Silico ◽  
Neuroprotective Effect ◽  
Monoamine Oxidase B ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mao B ◽  
Age Related ◽  
Novel Scaffold

Parkinson’s disease is an age related neurodegenerative disease. Pioglitazone is a Peroxisome proliferator-activated receptor gamma agonist that has been shown to display a neuroprotective effect in parkinsonian models (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated mice). This effect was partially attributed to the ability of thiazolidinedione (TZD) moiety in Pioglitazone to selectively inhibit monoamine oxidase B (MAO-B) enzyme. In the current study, we screened several thiazolidine containing compounds against MAO-B enzyme both in silico and in vitro. Based on the resulted data and information from previous literatures, we were able to design a novel scaffold for MAO-B inhibitors. This scaffold (compound 5482440) was able to inhibit MAO-B enzyme with IC50 value of 1.447 μM. Structure-based virtual analysis showed that this compound was able to participate in water-bridge formation and obtain an extended conformation within MAO-B active site.

STUDI IN SILICO DAN HUBUNGAN KUANTITATIF STRUKTUR TERHADAP AKTIVITAS TANAMAN MANGROVE (Avicennia marina (Forssk.) Vierh.) SEBAGAI ANTIDIABETES

2020 ◽  
Vol 2 (1) ◽  
pp. 112
Author(s):  
Arinil Hidayati ◽  
Siswandono Siswandono ◽  
Pramudita Riwanti
Keyword(s):  
Regression Analysis ◽  
In Silico ◽  
Avicennia Marina ◽  
Three Dimensions ◽  
Peroxisome Proliferator ◽  
Nonlinear Relationship ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molegro Virtual Docker ◽  
Relationship Of

The research is applied to 20 compounds contained  into <em>Avicennia marina</em> which is : <em>4’,5-dihydroxy-3’,5’,7-trimethoxyflavone, isorhamnetin 3-O-rutinoside, quercetin, stenocarproquinone B, avicennone C, avicennone E, avicennone F, avicennone D,   4’,5-dihydroxy-3’,7-dimethoxyflavone, chrysoeriol 7-O-glucoside, naphta(1,2-b)furan-4,5-dione, 3-hydroxy-naphta(1,2-b)furan-4,5-dione, kaempferol, 5-hydroxy-4’,7-dimethoxyflavone, avicequinone C, 2-[2’-(2’-hydroxy)propyl]-naphta[1,2-b]furan-4,5-dione, 4’,5,7-trihydroxyflavone, luteolin 7-O-methylether, luteolin 7-O-methylether 3’-O-beta-D-glucoside, 5,7-dihydroxy-3’,4’,5’-trimethoxyflavone</em> which are expected  to have an  effect as antidiabetics agent. It is undertaken to find out the linier or nonlinier relationship of  the structure activty (QSAR), the physicochemical characters (lipophilic, electronic, dan steric) to the activity changing (<em>rerank score</em>). Moreover, it is also undertaken to find out which one of those 20 <em>Avicennia marina </em>compounds are predicted to possess the activity as the best antidiabetics agent by the comparison of pioglitazon. It is arranged through computerized methods or <em>in silico</em> not only for having  the structure of two and three dimensions but also knowing the physicochemical characters too; through some programs such as  <em>ChemBioDraw Ultra </em>12.0 and <em>ChemBio3D Ultra </em>12.0 from <em>CambridgeSoft. The docking </em>program is used to make prediction of  the activity  by using <em>Molegro Virtual  Docker </em>2011.5.0.0 from CLCBio<em>.</em> by using the <em>peroxisome proliferator-activated receptor-gamma </em>(PPAR𝛾) in code of PDB: 2XKW. The result of the regression analysis through IBM SPSS program shows nonlinear relationship among structures, <em>Avicennia marina</em> physicochemical characters of twenty compound contents dealing with the activity changing. The compound of  <em>isorhamnetin 3-O-rutinoside</em><em>, chrysoeriol 7-O-glucoside, </em>and <em>luteolin 7-O-methylether 3’-O-beta-D-glucoside </em>are predicted to have the best antidiabetics agent if it is compared with the comparing drug pioglitazon.

IN SILICO DESIGN OF QUINOXALINE BEARING THIAZOLIDINONE DERIVATIVES AS PPARγ AGONIST IN DIABETES MELLITUS

2021 ◽  
pp. 47-50
Author(s):  
POORNIMA T ◽  
MANJU PT ◽  
ANJANA E
Keyword(s):  
Diabetes Mellitus ◽  
In Silico ◽  
Chemical Properties ◽  
Binding Pocket ◽  
Docking Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
In Silico Design ◽  
Lipinski’S Rule ◽  
Pparγ Agonist

Objective: Diabetes mellitus is a set of metabolic disease in which there is increased blood sugar level over a long period. The objective of the study is in silico design of quinoxaline bearing thiazolidinone derivatives as peroxisome proliferator-activated receptor gamma (PPARγagonist in diabetes mellitus. Methods: In silico design of proposed derivatives was conducted by ACD Lab ChemSketch 12.0 and derivatives obeying Lipinski’s rule of five were selected for docking studies. Docking was carried out using AutoDock Vina software. Results: Molinspiration results revealed that the designed derivatives had physical and chemical properties meant for an orally available drug. Based on the docking results derivatives, QNT1 and QNT2 exhibited high docking score which indicates that these derivatives possess high-affinity and high polar interaction toward protein 1PRG (ligand-binding domain of human peroxisome proliferator-activated receptor gamma). Conclusion: The designed quinoxaline bearing thiazolidinone derivatives were found to possess good binding affinity and good interaction in the binding pocket of target 1PRG, so these derivatives are expected to exhibit good antidiabetic property with minimal side effects.

An In Silico Approach Towards Investigation of Possible Effects of Essential oils Constituents on Receptors Involved in Cardiovascular Diseases (CVD) and Associated Risk Factors (Diabetes Mellitus and Hyperlipidemia)

2020 ◽  
Vol 18 ◽  
Author(s):  
Azadeh Hamedi ◽  
Amirhossein Sakhteman ◽  
Seyed Mahmoud Moheimani
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Side Effects ◽  
Essential Oils ◽  
In Silico ◽  
Data Bank ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Associated Risk Factors

Aim: Aromatherapy products, hydrosol beverages and distillates containing essential oils are widely used for cardiovascular conditions. Investigation of the possible activity of their major constituents with the cardiovascular related receptors may lead to develop new therapeutics. It also, may prevent unwanted side effects and drug-herb interactions. Materials and Methods: A list of 243 volatile molecule (mainly monoterpene and sesquiterpene) were prepared from literature survey in Scopus and PubMed (2000-2019) on hydrosols and essential oils which are used for cardiovascular diseases (CVD) and its risk factors (diabetes mellitus and hyperlipidemia). The PDB files of the receptors (229 native PDB files) included alpha glucosidase, angiotensin converting enzymes, beta-2 adrenergic receptor, glucocorticoid, HMGCoA reductase, insulin, mineralocorticoid, potassium channel receptors and peroxisome proliferator-activated receptor alpha, were downloaded from Protein Data Bank. An in silico study using AutoDock 4.2 and Vina in parallel mode was performed to investigate possible interaction of the molecules with the receptors. Drug likeliness of the most active molecules was investigated using DruLiTo software. Results: Spathulenol, bisabolol oxide A, bisabolone oxide, bergapten, bergamotene, dill apiole, pcymene, methyl jasmonate, pinocarveol, intermedeol, α-muurolol, S-camphor, ficusin, selinen-4- ol, iso-dihydrocarveol acetate, 3-thujanone, linanool oxide and cadinol isomers made a better interaction with some of the named receptors. All of the named molecules had an acceptable dug likeliness except for α-bergamotene. Also, all of the named molecules had the ability to pass the blood brain barrier and it is possible to produce unwanted side effects. Conclusion: Some ingredients of essential oils might be active on cardiovascular related receptors.

scholarly journals Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

2021 ◽  
Vol 22 (13) ◽  
pp. 6907
Author(s):  
Maria L. Lozano ◽  
Cristina Segú-Vergés ◽  
Mireia Coma ◽  
María T. Álvarez-Roman ◽  
José R. González-Porras ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
In Silico ◽  
Immune Thrombocytopenia ◽  
Transforming Growth Factor ◽  
Direct Action ◽  
Cell Types ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mediated Effects ◽  
Primary Immune Thrombocytopenia

Eltrombopag is a thrombopoietin receptor (MPL) agonist approved for the treatment of primary immune thrombocytopenia (ITP). Recent evidence shows that some patients may sustain platelet counts following eltrombopag discontinuation. The systemic immunomodulatory response that resolves ITP in some patients could result from an increase in platelet mass, caused either by the direct action of eltrombopag on megakaryocytes through MPL stimulation, or potential MPL-independent actions on other cell types. To uncover the possible mechanisms of action of eltrombopag, in silico analyses were performed, including a systems biology-based approach, a therapeutic performance mapping system, and structural analyses. Through manual curation of the available bibliography, 56 key proteins were identified and integrated into the ITP interactome analysis. Mathematical models (94.92% mean accuracy) were obtained to elucidate potential MPL-dependent pathways in non-megakaryocytic cell subtypes. In addition to the effects on megakaryocytes and platelet numbers, the results were consistent with MPL-mediated effects on other cells, which could involve interferon-gamma, transforming growth factor-beta, peroxisome proliferator-activated receptor-gamma, and forkhead box protein P3 pathways. Structural analyses indicated that effects on three apoptosis-related proteins (BCL2L1, BCL2, BAX) from the Bcl-2 family may be off-target effects of eltrombopag. In conclusion, this study proposes new hypotheses regarding the immunomodulatory functions of eltrombopag in patients with ITP.

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