SYNTHESIS AND DOCKING STUDIES OF 2-(NITROOXY)-ETHYL-2-(SUBSTITUTED-2,5-DIPHENYL-OXAZOLE)-ACETATE AS ANTI-INFLAMMATORY AGENTS WITH ANALGESIC AND NITRIC OXIDE RELEASING PROPERTIES

Objective: The objective of the reported study was to develop new chemical entities as potential anti-inflammatory agents with analgesic and nitric oxide releasing properties.Methods: The compounds were designed with the help of docking studies. In the synthetic study the target compounds were obtained by reacting 2-(substituted-2,5-diphenyl-oxazole)-acetic acid (2a-2v) with nitro-oxy ethyl bromide in the presence of dimethyl formamide and potassium carbonate to give 2-(nitrooxy) ethyl 2-(substituted-2,5-diphenyl-oxazole) acetate derivatives (3a-3v). The synthesized derivatives were characterized with the help of different analytical techniques and further evaluated for anti-inflammatory, analgesic and nitric oxide releasing activity.Results: With the help of docking study it was proven that compounds 3a, 3c, 3g, 3l and 3r showed significant G-score. In the anti-inflammatory and analgesic study also, compounds 3a, 3c, 3g, 3l and 3r exhibited promising activity. All the synthesized compounds exhibited significant nitric oxide releasing properties both in-vitro and in-vivo. Conclusion: Compounds 3a, 3c, 3g, 3l and 3r exhibited prominent anti-inflammatory and analgesic activity.Â

Relationship of umbilical coiling index and cord twist direction with adverse perinatal outcomes

Background: The main objectives of this study were to examine - (1) relationship of pregnancy-related factors (maternal age, gestational diabetes mellitus, pregnancy-induced hypertension, oligohydramnios, small for gestational age (GA), and fetal gender) and postnatally measured umbilical coiling index (UCI); (2) association of UCI and cord twist directions with the following adverse perinatal outcomes, meconium staining of amniotic fluid, non-reassuring FHR on CTG, low Apgar score ( 34 weeks. The cases were categorized in hypocoiled (UCI 90th percentile) and normocoiled groups. To study relationship of pregnancy-related factors and UCI multivariate logistic regression was used; whereas bivariate analysis was used to study impact of UCI on various adverse perinatal outcomes. UCI was measured by a single observer.Results: In total, 100 subjects were enrolled. The mean UCI was 0.268 (SD = 0.13; 10th percentile = 0.139; 90th percentile =0.410) coils/cm. Pregnancy-related factors had non-significant relationship with UCI. For adverse perinatal outcomes, only the non-reassuring/abnormal FHR patterns were significantly associated with hypercoiled groups (OR = 4.5; CI= 1.15-17.58). Both the cord directions had almost equal distribution without any significant difference in outcomes; however, anticlockwise twisted cords were found to have significantly high UCI.Conclusions: No significant relationship was observed with pregnancy-related factors and UCI. However, it was observed that hypercoiled cords had significant association with non-reassuring/abnormal FHR patterns on CTG

Data Doctor: An Efficient Data Profiling and Quality Improvement Tool

Many business and IT managers face the same problem: the data that serves as the foundation for their business applications inconsistent,inaccurate,and unreliable. Data profiling is the solution to this problem and, as such, is a fundamental step that should begin every data-driven initiative.In this paper we have implemented the technique of data profiling such as Column Analysis,Frequency Analysis, Null Rule Analysis,Constant Analysis, Empty Column Analysis and Unique Analysis. DOI: 10.17762/ijritcc2321-8169.160411

SYNTHESIS AND DOCKING STUDIES OF 2-(NITROOXY) ETHYL-4-(2-(SUBSTITUTED PHENYL)-4-(SUBSTITUTE DPHENYL)-1H-IMIDAZOL-1-YL) BENZOATE AS ANTI-INFLAMMATORY, ANALGESIC AND NITRIC OXIDE RELEASING AGENTS

Objective: The objective of the present study was to develop potent and non toxic Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) by using heterocyclic nuclei and having Nitric Oxide releasing group.Methods: The compounds were designed with the help of docking studies. In the synthetic study, the target compounds were obtained by reacting substituted diphenyl imidazole benzoic acid (2a-2x) with nitro-oxy alkyl bromide in the presence of dimethyl formamide and potassium carbonate to give substituted 2,4-diphenyl nitric oxide releasing imidazole derivatives (3a-3x). The synthesized compounds were characterized with the help of different analytical studies and further evaluated for anti-inflammatory, analgesic and nitric oxide releasing activity.Results: In the docking study compounds 3a, 3b, 3c, 3e, 3r and 3s showed significant G-score. In the anti-inflammatory and analgesic study compounds 3a, 3b, 3c, 3e, 3r and 3s exhibited promising activity. All the synthesized compounds exhibited significant nitric oxide releasing properties both in-vitro and in-vivo. Conclusion: Compounds 3a, 3b, 3c, 3e, 3r and 3s exhibited prominent anti-inflammatory and analgesic activity.Â

Alum [KAl(SO4)2•12H2O] catalyzed microwave assisted synthesis of 5-arylidine-2-(methylthio)-thiazolone derivatives in water

An efficient and environmentally benign method has been developed for the synthesis of 5-arylidine-2-(methylthio)-thiazolones derivatives using Alum [KAl(SO4)2·12H2O] catalyst and triethyl amine in water under microwave irradiation. This green transformation generated one C-S and one C-C bond, condensation and S-methylation. Notable advantages for the present protocol include, short reaction time, cleaner reaction profile and easy isolation of product by microwave irradiation technique using green catalyst and solvent

Synthesis and antiproliferative evaluation of new (4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methane substituted sulfonamide derivatives

A series of new molecules having 4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methane substituted sulfonamide derivatives were synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, Mass spectra, and the purity was checked through HPLC analysis. The compounds were also evaluated for their in vitro antiproliferative activity against MCF-7, HeLa, A-549 and DU-145 cancer cell lines by MTT assay. Compounds 4d, 7c and 7d were tested for their activity against a panel of eight human kinase at 10 µM concentrations. Among them the compounds 4d and 7d showed very promising activity against CDK5/P25 kinase with 66 and 70% inhibitions, respectively. Compound 7c also showed promising activity of 59% inhibition. The preliminary bioassay showed that most of the compounds were antiproliferative with different degrees, and some compounds showed better activity than 5-fluorouracil which was used as positive control

Structure-Based Site of Metabolism (SOM) Prediction of Ligand for CYP3A4 Enzyme: Comparison of Glide XP and Induced Fit Docking (IFD)

Metabolism is one of the prime reasons where most of drugs fail to accomplish their clinical trials. The enzyme CYP3A4, which belongs to the superfamily of cytochrome P450 enzymes (CYP), helps in the metabolism of a large number of drugs in the body. The enzyme CYP3A4 catalyzes oxidative chemical processes and shows a very broad range of ligand specificity. The understanding of the compound’s structure where oxidation would take place is crucial for the successful modification of molecules to avoid unwanted metabolism and to increase its bioavailability. For this reason, it is required to know the site of metabolism (SOM) of the compounds, where compounds undergo enzymatic oxidation. It can be identified by predicting the accessibility of the substrate’s atom toward oxygenated Fe atom of heme in a CYP protein. The CYP3A4 enzyme is highly flexible and can take significantly different conformations depending on the ligand with which it is being bound. To predict the accessibility of substrate atoms to the heme iron, conventional protein-rigid docking methods failed due to the high flexibility of the CYP3A4 protein. Herein, we demonstrated and compared the ability of the Glide extra precision (XP) and Induced Fit docking (IFD) tool of Schrodinger software suite to reproduce the binding mode of co-crystallized ligands into six X-ray crystallographic structures. We extend our studies toward the prediction of SOM for compounds whose experimental SOM is reported but the ligand-enzyme complex crystal structure is not available in the Protein Data Bank (PDB). The quality and accuracy of Glide XP and IFD was determined by calculating RMSD of docked ligands over the corresponding co-crystallized bound ligand and by measuring the distance between the SOM of the ligand and Fe atom of heme. It was observed that IFD reproduces the exact binding mode of available co-crystallized structures and correctly predicted the SOM of experimentally reported compounds. Our approach using IFD with multiple conformer structures of CYP3A4 will be one of the effective methods for SOM predictionAuthor A.P.S. is grateful to the University Grants Commission, New Delhi for the financial assistance under the major research project (42-677/2013 (SR)) and Dr. Babasaheb Ambedkar Marathwada University, Aurangabad for the research grant (STAT/VI/RG/Dept/2019-20/309-10)S

Interacting Two Fluid Viscous Dark Energy Cosmological Models in Bianchi Type II Universe

In this paper, we present a class of solutions of Barber’s second self creation field equations describing two fluid models of the universe in locally rotationally symmetric Bianchi type II universe filled with the barotropic fluid and bulk viscous dark energy fluid. Exact solutions of the field equations are obtained for non-interacting and interacting two fluid models. The Physical behavior of the model has been discussed

Magnetized Anisotropic Dark Energy Bianchi Type III Cosmological Models in Brans-Dicke Theory of Gravitation

We investigate the spatially homogeneous Bianchi Type III cosmological models with magnetized anisotropic dark energy fluid in the scalar tensor theory of gravitation proposed by Brans-Dicke [1]. The solutions of the models are obtained by volumetric exponential expansion, power law expansion and power law relation between scalar field and scale factor ‘a’. The physical aspects of the dark energy models are discussed

An alum [KAl (SO4)2.12H2O] catalyzed microwave assisted multicomponent synthesis of bioactive functionalized benzylpyrazolyl coumarin and quinolinone derivatives in PEG

An efficient and environmentally benign method has been developed for the synthesis of benzylpyrazolyl coumarin and quinolinone derivatives, hydroxy coumarin derivatives using Alum [KAl (SO4)2.12H2O] catalyst and Polyethylene glycol as green solvent under microwave condition. Keywords: Knoevenagel, Michael addition reaction, coumarins, quinolinones, alum, polyethylene glycol, multicomponent microwave irradiation method