DESIGN OF NEW PEROXISOME PROLIFERATORS GAMMA ACTIVATED RECEPTOR AGONISTS (PPARγ) VIA QSAR BASED MODELING

The Peroxisome proliferators-activated receptors (PPARs) are one of the nuclear fatty acid receptors, which contain a type II zincfinger DNA binding pattern and a hydrophobic ligand binding pocket. These receptors are thought to play an essential role in metabolic diseasessuch as obesity, insulin resistance, and coronary artery disease. Therefore Peroxisome Proliferators-Activated Receptor (PPARγ) activators havedrawn great recent attention in the clinical management of type 2 diabetes mellitus, prompting several attempts to discover and optimize newPPARγ activators. Objective: The aim of the study was to finding new selective human PPARγ (PPARγ) modulators that are able to improveglucose homeostasis with reduced side effects compared with TZDs and identify the specific molecular descriptor and structural constraint toimprove the agonist activity of PPARγ analogs. Material and Method: Software’s that was used for this study include S.P. Gupta QSARsoftware (QSAR analysis), Valstat (Comparative QSAR analysis and calculation of L-O-O, Q2, r2, Spress), BILIN (Comparative QSAR analysisand calculation of Q2, r, S, Spress, and F), etc., allowing directly performing statistical analysis. Then multiple linear regression based QSARsoftware (received from BITS-Pilani, India) generates QSAR equations. Result and Discussion: In this study, we explored the quantitativestructure–activity relationship (QSAR) study of a series of meta-substituted Phenyl-propanoic acids as Peroxisome Proliferators Gamma activatedreceptor agonists (PPARγ).The activities of meta-substituted Phenyl-propanoic acids derivatives correlated with various physicochemical, electronic and steric parameters.Conclusion: The identified QSAR models highlighted the significance of molar refractivity and hydrophobicity to the biological activity.

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Evaluation of contribution of different molecular fragments on antibacterial activity of Schiff bases of indole-3-aldehyde based on QSAR study

Canadian Journal of Chemistry ◽

10.1139/cjc-2013-0122 ◽

2013 ◽

Vol 91 (12) ◽

pp. 1174-1178

Author(s):

Priyanka Kamaria ◽

Neha Kawathekar

Keyword(s):

Antibacterial Activity ◽

Schiff Bases ◽

Positive Contribution ◽

Qsar Study ◽

Qsar Analysis ◽

Modeling Software ◽

Qsar Models ◽

Leave One Out ◽

3D Package ◽

Dipole Energy

The paper describes the QSAR analysis of a series of 22 Schiff bases of indole-3-aldehyde employing the Hansch approach. Various physicochemical and steric parameters were calculated using the Chem 3D package of molecular modeling Software Chemoffice 2004. QSAR models were generated employing the sequential multiple regression method. Models were validated using leave-one-out and bootstrapping methods. Results obtained show that dipole–dipole energy, LUMO, and total energy play an important role, as their positive contribution is seen in the models. Findings of the present study reveal that substituents that cause increase in flexibility, a decrease in polarity, and electron withdrawing in nature are favorable for antibacterial activity of Schiff bases.

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QSAR analysis and molecular docking study of pyrrolo- and pyridoquinolinecarboxamides with diuretic activity

ScienceRise Pharmaceutical Science ◽

10.15587/2519-4852.2021.234493 ◽

2021 ◽

pp. 19-27

Author(s):

Mykola Golik ◽

Tetiana Titko ◽

Angelina Shaposhnyk ◽

Marharyta Suleiman ◽

Iryna Drapak ◽

...

Keyword(s):

Molecular Docking ◽

Carbonic Anhydrase ◽

De Novo ◽

Molecular Descriptor ◽

External Validation ◽

Docking Study ◽

Quinoline Derivatives ◽

Diuretic Activity ◽

Qsar Analysis ◽

Qsar Models

The aim. The aim of the study was to reveal QSAR and ascertain the possible mechanism of action via docking study in the row of tricyclic quinoline derivatives with diuretic activity. Materials and methods. Pyrrolo- and pyridoquinolinecarboxamides with proven diuretic activity were involved in the study. Molecular descriptors were calculated using HyperChem and GRAGON software, and QSAR models were built using BuildQSAR software. For receptor-oriented flexible docking, the Autodock 4.2 software package was used. Results. Multivariate linear QSAR models were built on two datasets of quinolinecarboxamides: Vol = a∙X1 + b∙X2 + c∙X3 + d, where Vol – volume of the daily produced urine in rats, Xi – molecular descriptor. QSAR analysis showed that the diuretic activity is determined by the geometric and spatial structure of molecules, logP, the energy values, RDF- and 3D-MoRSE-descriptors. Based upon internal and external validation of the models, the most informative two-parameter linear QSAR model 3а was proposed. Docking data showed the high affinity of two lead compounds to the carbonic anhydrase II. Conclusions. QSAR analysis of tricyclic quinoline derivatives revealed that the diuretic activity increases with the increase of value of logP, refractivity, and dipole moment and with the decrease of volume, surface area, and polarization of the molecules. Increase of values of such energy descriptors as bonds energy, core-core interaction, and energy of the highest occupied molecular orbital results in higher diuresis; decrease in hydration energy leads to higher diuretic activity. Based upon molecular docking calculation, the mechanism of diuretic action is proposed to be carbonic anhydrase inhibition. QSAR models and docking data are useful for in-depth study of diuretic activity of tricyclic quinolines and could be a theoretical basis for de novo-design of new diuretics

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Abstract #212 Association of Serum Insulin and Urinary Albumin with Occult Coronary Artery Disease in Patients with Type-2 Diabetes Mellitus

Endocrine Practice ◽

10.1016/s1530-891x(20)47058-2 ◽

2018 ◽

Vol 24 ◽

pp. 33-34

Author(s):

Sudhir Bhandari ◽

Senior ◽

Banshi Saboo ◽

Shashank Joshi

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Type 2 Diabetes Mellitus ◽

Coronary Artery ◽

Serum Insulin ◽

Urinary Albumin ◽

Artery Disease

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547 Stress myocardial scintigraphy and dobutamine echocardiography in the detection of coronary artery disease in asymptomatic patients with type 2 diabetes

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(04)90411-0 ◽

2004 ◽

Vol 3 (1) ◽

pp. 142

Author(s):

C LEFEUVRE

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Myocardial Scintigraphy ◽

Dobutamine Echocardiography ◽

Asymptomatic Patients ◽

Artery Disease

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Evaluation of aortic arch calcification in type 2 diabetic patients

VASA ◽

10.1024/0301-1526.34.2.113 ◽

2005 ◽

Vol 34 (2) ◽

pp. 113-117 ◽

Cited By ~ 4

Author(s):

Papanas ◽

Symeonidis ◽

Maltezos ◽

Giannakis ◽

Mavridis ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Aortic Arch ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Insulin Dependence ◽

Artery Disease ◽

Type 2 Diabetic ◽

Aortic Arch Calcification

Background: The purpose of this study is to evaluate the severity of aortic arch calcification among type 2 diabetic patients in association with diabetes duration, diabetic complications, coronary artery disease and presence of cardiovascular risk factors. Patients and methods: This study included 207 type 2 diabetic patients (101 men) with a mean age of 61.5 ± 8.1 years and a mean diabetes duration of 13.9 ± 6.4 years. Aortic arch calcification was assessed by means of posteroanterior chest X-rays. Severity of calcification was graded as follows: grade 0 (no visible calcification), grade 1 (small spots of calcification or single thin calcification of the aortic knob), grade 2 (one or more areas of thick calcification), grade 3 (circular calcification of the aortic knob). Results: Severity of calcification was grade 0 in 84 patients (40.58%), grade 1 in 64 patients (30.92%), grade 2 in 43 patients (20.77%) and grade 3 in 16 patients (7.73%). In simple regression analysis severity of aortic arch calcification was associated with age (p = 0.032), duration of diabetes (p = 0.026), insulin dependence (p = 0.042) and presence of coronary artery disease (p = 0.039), hypertension (p = 0.019), dyslipidaemia (p = 0.029), retinopathy (p = 0.012) and microalbuminuria (p = 0.01). In multiple regression analysis severity of aortic arch calcification was associated with age (p = 0.04), duration of diabetes (p = 0.032) and presence of hypertension (p = 0.024), dyslipidaemia (p = 0.031) and coronary artery disease (p = 0.04), while the association with retinopathy, microalbuminuria and insulin dependence was no longer significant. Conclusions: Severity of aortic arch calcification is associated with age, diabetes duration, diabetic complications (retinopathy, microalbuminuria), coronary artery disease, insulin dependence, and presence of hypertension and dyslipidaemia.

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