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.

scholarly journals IN SILICO DESIGN OF BENOXAZOLE BEARING AZETIDINONE DERIVATIVES AS VEGFR-2 AGONIST IN CANCER

2021 ◽  
pp. 112-115
Author(s):  
LEYANA PN ◽  
MANJU PT ◽  
MEENU VIJAYAN
Keyword(s):  
In Silico ◽  
Chemical Properties ◽  
Binding Pocket ◽  
Docking Studies ◽  
Vascular Endothelial ◽  
In Silico Design ◽  
Lipinski’S Rule ◽  
Orally Bioavailable ◽  
Endothelial Growth Factor ◽  
Physical And Chemical

Objective: Cancer is a group of disease characterized by uncontrolled growth of cells. The objective of the study includes the in silico designing of benzoxazole bearing azetidinone derivatives as Vascular Endothelial Growth Factor 2 in cancer. Methods: In silico design of proposed derivatives was conducted using tools such as AutoDock Vina, ACD Lab ChemSketch ver. 12.0, Prediction of Activity Spectra for Substances online, molinspiration, and Swiss ADME. The derivatives obeying Lipinski’s Rule of Five in accordance with molinspiration were selected for docking studies. Results: The data obtained from molinspiration revealed that the designed derivatives have physical and chemical properties meant for an orally bioavailable drug. From the docking studies derivatives BT1 and BT5 showed high docking score which indicate that these derivatives possess high affinity and high polar interaction towards protein 4DBN. Conclusion: The designed benzoxazole bearing azetidinone derivatives were found to possess good binding affinity and good interaction in the binding pocket of the target 4DBN. Therefore, these derivatives are expected to exhibit good anticancer property with minimal side effects.

scholarly journals Newly Synthesized Oxadiazole Based Mannich Base Derivatives of Fatty Acid: in Silico Study and in Vivo Anti-Hyperglycaemic Estimation

2018 ◽  
Vol 34 (5) ◽  
pp. 2253-2267 ◽  
Author(s):  
Garima Kapoor ◽  
Dharam Pal Pathak ◽  
Rubina Bhutani ◽  
Asif Husain ◽  
Sandeep Jain ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Active Sites ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Energy Estimation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipinski’S Rule

A receptor peroxisome proliferator activated receptor-gamma was targeted by series of new fatty acid chemical entities (M1- M22) which was designed, synthesized and characterized by spectral analysis. Metabolites molecular properties were calculated using Lipinski’s rule of five using molinspiration online software. Docking studies were done on co-crystallized protein structure of PPAR γ, PDB-1FM9 showing M15, M17 and M8 to be best located in the active sites with scores -10.43, -10.21 and -10.00 respectively. The free binding energy estimation was done using model of Maestro 9.0 (Schrodinger) and lies between -80.15 to -61.26 kcal/mol which is significant as compared to that of standard (-48.58 Kcal/mol). Nine best docked derivatives were evaluated in-vivo for oral glucose tolerance and antihyperglycemic activity by streptozotocin induced diabetes model and M15 exhibited most promising antidiabetic activity more than the standard glibenclamide. The promising results encourage future investigation on fatty acids for development of active compounds.

Pioglitazone prevents cardiac remodeling in high-fat, high-calorie-induced Type 2 diabetes mellitus

2006 ◽  
Vol 291 (1) ◽  
pp. H81-H87 ◽  
Author(s):  
Walter E. Rodriguez ◽  
Irving G. Joshua ◽  
Jeff C. Falcone ◽  
Suresh C. Tyagi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Left Ventricular ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Calorie Diet

The agonists of peroxisome proliferator-activated receptor-γ (PPARγ) ameliorate cardiovascular complications associated with diabetes mellitus. We tested the hypothesis that recovery from ailing to failing myocardium in diabetes by PPARγ agonist is in part due to decreased matrix metalloproteinase-9 (MMP-9) activation and left ventricular (LV) tissue levels of homocysteine (Hcy). C57BL/6J mice were made diabetic (D) by feeding them a high-fat calorie diet. PPARγ was activated by adding pioglitazone (Pi) to the diet. After 6 wk, mice were grouped into: normal calorie diet (N), D, N + Pi and D + Pi ( n = 6 in each group). LV variables were measured by echocardiography, endothelial-myocyte (E-M) coupling was measured in cardiac rings, and MMP-9 activation was measured by zymography. Blood glucose levels were twofold higher in D mice compared with N mice. Pi decreased the levels of glucose in D mice to the levels in N mice. LV Hcy levels were 3.5 ± 0.5 μM in N groups compared with 12.4 ± 0.6 μM in D groups. Treatment with Pi normalized the LV levels of Hcy but had no effect on plasma levels of Hcy. In the D group, LV contraction was reduced compared with that of the N group and was ameliorated by treatment with Pi. LV wall thickness was reduced to 0.25 ± 0.02 mm in the D group compared with 0.42 ± 0.01 mm in the N group. LV diastolic diameter was 3.05 ± 0.01 mm in the D group compared with 2.20 ± 0.02 mm in the N group. LV systolic diameter was 1.19 ± 0.02 mm in the D group and 0.59 ± 0.01 mm in the N group. Pi normalized the LV variables in D mice. The responses to ACh and nitroprusside were attenuated in diabetic hearts, suggesting that there was E-M uncoupling in the D group compared with the N group, which was ameliorated by Pi. Plasma and LV levels of MMP-2 and -9 activities were higher in the D group than in the N group but normalized after Pi treatment. These results suggest that E-M uncoupling in the myocardium, in part, is due to increased MMP activities secondary to suppressing PPARγ activity in high-fat, calorie-induced Type 2 diabetes mellitus.

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 Design and synthesis of novel heterocyclic compounds as a PPAR-γ agonist

2020 ◽  
Vol 11 (2) ◽  
pp. 2063-2069
Author(s):  
Zambare Y. B. ◽  
Bhole R. P. ◽  
Chitlange S. S.
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Ppar Γ

The multifarious metabolic syndrome, diabetes mellitus (DM), is a diseaseof concern all over the world and is approximate to affect 400 million individuals by the 2020. Several classes of drugs at the moment are available to lessen hyperglycemia in diabetes mellitus especially in Type-II. These drugs mostly have dangerous side effects and thus incisive for a new class of compounds is necessary to conquer this inconvenience. A series of 6 novel 5-nitrobenzofuran-2yl-carbamides derivatives were synthesized and molecular docking studies were performed on PPAR-γ target using (PDB code-4rfm).The preparation of5-nitro-1-benzofuran-2-carbohydrazide(4) on action with acetic acid, 1, 4-diaxone and sodium nitrite resulted in 5-nitro-1-benzofuran-2-carbonyl azide (5).The related compound (5) on action with substituted aromatic substituted amines undergoes Curtis type of rearrangement to give 5-nitro-N-(sub. carbamoyl)-1-benzofuran-2-carboxamide.The characterization and identification of prepared compounds were identified on the basis of NMR, IR, Mass and elemental analysis. Docking study of targeted compounds were done using software Autodock Tools 1.5.6 and visualisation done by Discovery Studio 3.5 software (Accelrys Inc. San Diego, CA USA). Molecular docking studies, the binding energies are determined to be in the range of –5.90 to –9.80 kcal/mol, with peroxisome proliferator activated receptor γ (PPAR-γ) receptors (PDB ID: 4RFM). The prepared compounds have been studied for their oral glucose tolerance test to distinguish the effect on plasma glucose level.

scholarly journals Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus

2002 ◽  
pp. 545-551 ◽  
Author(s):  
M Bluher ◽  
T Klemm ◽  
T Gerike ◽  
H Krankenberg ◽  
G Schuler ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Multiple Logistic Regression Analysis ◽  
Peroxisome Proliferator ◽  
Haemoglobin A1c ◽  
Peroxisome Proliferator Activated Receptor ◽  
Patients With Diabetes ◽  
Reduced Risk

OBJECTIVE: Recent evidence indicates that peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed at high levels in foam cells of atherosclerotic lesions, that PPARgamma agonists may directly modulate vessel wall function and that mutations in the PPARgamma-2 gene are associated with a reduced risk of coronary artery disease. METHODS: We investigated whether known variants in the PPARgamma-2 gene are associated with the occurrence of coronary heart disease (CHD) in 365 patients with type 2 diabetes, prospectively characterised for the presence or absence of CHD. The Pro115Gln, Pro12Ala, Pro467Leu, Val290Met mutations and two polymorphisms C478T and C161T of the PPARgamma-2 gene were examined using PCR, denaturing gradient gel electrophoresis and direct sequencing. RESULTS: The distribution of the Pro12Ala, Ala12Ala, C161T and T161T variants was not significantly different between patients with and without CHD, independent of the gender. The Pro12Ala (P=0.011) and the Ala12Ala (P=0.006) variant were associated with a higher body mass index (BMI) compared with the Pro12Pro genotype. A multiple logistic regression analysis introducing the typical risk factors for CHD (age, sex, hypertension, smoking, BMI >26 kg/m2, elevated low density lipoprotein cholesterol and haemoglobin A1c >7%) identified age >60, male gender, hypertension and a higher BMI, but not the PPARgamma-2 variants, as significant risk factors for CHD in our study groups. CONCLUSION: The PPARgamma-2 genotype was not associated with an increased or reduced risk of the occurrence of CHD and can therefore not be regarded as an independent risk factor for CHD in patients with diabetes mellitus.

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