(1) This document describes research into generating molecular diversity from cyclooctatetraene (COT) and testing the inhibitory activity of generated compounds against β-glucosidase.
(2) COT is reacted with electrophiles like H+ and PhCO+ to form diverse products via reaction of (COT)Fe(CO)3. Over 10 steps, several aminocycloheptitol compounds were synthesized in 15-26% overall yields.
(3) The inhibitory activities of these compounds were tested against β-glucosidase. Several compounds showed IC50 values in the low micromolar to millimolar range, with one compound having an IC50 of 41.66 μM.
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National Institute of Pharmaceutical Education and Research Mohali, Punjab-160062 (India)
Mail ID- 20mcm_prashant@niper.ac.in
GABA spectroscopy
edited GABA 1H MEGA-PRESS spectra
GABA-edited
In this study, we have developed and demonstrated a non-water suppressed GABA editing Magnetic Resonance Spectroscopic Imaging technique using density-weighted concentric rings k-space trajectory that performs robustly within a clinically feasible acquisition time at 3T. The method has been validated in a series of phantom experiments and its feasibility assessed in a healthy volunteer with a high in-plane resolution of 7.5 × 7.5 mm. Experiments qualitatively demonstrate the advantage of the proposed method in terms of its improved resolution and reduced contamination of spectra from neighboring voxels.
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Noninvasive assessment of isocitrate dehydrogenase mutation
2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma
2-Hydroxyglutarate as a Magnetic Resonance Biomarker for Glioma
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RSNA
Wellcome Centre for Integrative Neuroimaging
FMRIB
Purdue
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Prashant Chavan (GPAT,NIPER Qualified)
M.S. (Pharm) in Medicinal Chemistry
National Institute of Pharmaceutical Education and Research Mohali, Punjab-160062 (India)
Mail ID- 20mcm_prashant@niper.ac.in
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Synthesis, Characterization, and Antibacterial Activity of Some Novel 5-Chlor...IJERA Editor
The development of potential antibacterial requires the synthesis of a new series of 5- Chloroisatin derivatives incorporating various aromatic aldehydes in the case 1,3-Dipolar Cycloaddition including Nitrile oxide, as well as the cycloaddition Alcyne-Azide Catalytic with Copper. The charcterization of the structure of the synthesized compounds was confirmed by means of their IR, 1H-NMR and 13C-NMR spectral data. In addition, the antibacterial properties in vitro were tested against certain microorganisms using the disk diffusion technique. A majority of compounds show better activity against several of the microorganisms.
A Statistical Approach to Optimize Parameters for Electrodeposition of Indium...Arkansas State University
A Statistical Approach to Optimize Parameters for Electrodeposition of Indium (III) Sulfide Films, Potential Low-Hazard Buffer Layers for Photovoltaic Applications
STUDIES ON INTEGRATED BIO-HYDROGEN PRODUCTION PROCESS-EXPERIMENTAL AND MODELINGArghya_D
In the project “Studies on integrated biohydrogen production process-Experimental and Modeling”,a co-culture (mixture of two microorganisms in a single reactor) study of a dark fermentative and photofermentative microorganism was done to assess its hydrogen production performance. For modeling purpose, Artificial Neural Network and Genetic Algorithm has been used as a stochastic technique. The optimized data from batch study was successfully used to run a photobioreactor in continuous mode. A mechanistic model was developed for a continuous co-culture setup using data from literature and solved using MATLAB.
Generation of Diverse Molecular Complexity from cyclooctatetraene_defense
1. Generation Of Diverse Molecular Complexity
From Cyclooctatetraene
Marquette University
By
Mohamed El Mansy
04/03/2014
2. Diversity-oriented synthesis
Preparation of structurally complex and
diverse compounds from simple starting
materials.
Lee, D.; Sello, J. K.; Schreiber, S. L. Org. Lett., 2000, 2, 709-712.
3. How to generate molecular
diversity?
Reagent-based approach
Common starting material
Substrate-based
approach
Common reagents
Diversity-Oriented Synthesis: Basics and Applications in Organic Synthesis, Drug Discovery, and Chemical Biology, 2013 John Wiley & Sons, Inc.
4. Cyclooctatetraene (COT)
Simple compound C8H8.
Commercially available.
Reppe, W.; Schichting, O.; Klager, K.; Toepel, T. Ann 1948, 560, 1-92. Barnes, C. E. U.S. Patent 2 579
106, 1951.
Shvo, Y.; Hazum, E. J. Chem. Soc., Chem. Comm. 1975, 829-830.
5. Reaction of (COT)Fe(CO)3 with electrophiles
El= H+
El= PhCO+
Broadley, K.; Connelly, N. G.; Graham, P. G.; Howard, J. A. K.; Risse, W.; Whiteley, M. W.; Woodward, P. J. Chem. Soc. Dalton
Charles, A. D.; Diversi, P.; Johnson, B. F. G.; Karlin, K. D.; Lewis, Rivera, A. V.; Scheldrick, G. M. J. Organomet. Chem.
1977, 128, C31-C34.
Davison, A.; McFarlane, W.; Pratt, L.; Wilkinson, G. J. Chem. Soc. 1962,
4821-4829.
6. Mechanism for formation
Broadley, K.; Connelly, N. G.; Graham, P. G.; Howard, J. A. K.; Risse, W.; Whiteley, M. W.; Woodward, P. J. Chem. Soc. Dalton
Charles, A. D.; Diversi, P.; Johnson, B. F. G.; Karlin, K. D.; Lewis, Rivera, A. V.; Scheldrick, G. M. J. Organomet. Chem.
1977, 128, C31-C34.
El= H+
El= PhCO+
8. Glycosidic bond
The glycosidic bond is very stable towards
hydrolysis.
Glycosidase enzymes catalyze the hydrolysis
reaction. glycosidic linkage.
http://www.chem.qmul.ac.uk/iupac/2carb/33.ht
9. Glycosidase inhibitors
Hydrolysis of glycosidic bond with retention of configuration at anomeric carbon.
Zechel, D. L.; Withers, S. G. Acc. Chem. Res. 2000, 33, 11-18.
10. Examples of known aminocyclitols
Hooper, R. In “Aminoglycoside Antibiotics”; Umezawa, H., Hooper, I. R., Eds.; Springer, Berlin,
1981; p 7.
Girard, E.; Desvergnes, V.; Tarnus, C.; Landais, Y. Org. Biomol. Chem. 2010, 8,
5628–5634.
Casiraghi, G. et. Al. J. Org. Chem., 2003, 68, 5881-5885.
35. Generated Tetraols
Out of 16 possible isomers, we synthesized 8.
Assignments were made by NMR and single crystal X-ray
diffraction.
36. Testing of the generated
tetraols
β-Glucosidase was selected as enzyme to be
initially testing the protected bicyclic tetraols.
Validation of assay is done by using different
enzyme concentrations.
Testing a known inhibitor and reproduce inhibition
data.
determined colorimetrically
37. Glucosidase Validation Curve
y = 0.0002x + 0.0132
R² = 0.9995
y = 2E-05x - 0.0028
R² = 0.9676
y = 0.0005x + 0.029
R² = 0.9991
y = 0.0009x + 0.0635
R² = 0.9984
y = 0.0012x + 0.0959
R² = 0.9974
y = 0.0022x + 0.1012
R² = 0.9989
y = 0.0017x + 0.1217
R² = 0.9993
-0.05
0
0.05
0.1
0.15
0.2
0.25
0.3
0 50 100 150 200 250
Absorbance(406nm)
Time (s)
Glucosidase Validation Curve
6…
38. Assay Results
-5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
7 0
8 0
9 0
1 0 0
1 1 0
M M L 2 8 6 _ f1 D o s e R e s p o n s e (4 p t)
lo g ([X ],M )
%Act
IC50=1.68mM
-5 .5 -5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
6 0
7 0
8 0
9 0
1 0 0
1 1 0
M M L 2 8 6 _ f2 D o s e R e s p o n s e
lo g ([X ],M )
%Activity
IC50= 156.8µM
39. -5 .5 -5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
7 0
8 0
9 0
1 0 0
1 1 0
M M L 3 2 6 _ f2 D o s e R e s p o n s e
lo g ([X ],M )
%Activity
IC50= 41.66µM
-5 .5 -5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
7 0
8 0
9 0
1 0 0
1 1 0
M M L 2 7 8 _ f2 D o s e R e s p o n s e
lo g ([X ],M )
%Act.
IC50= 1.904mM
Assay Results
40. -5 .5 -5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
7 0
8 0
9 0
1 0 0
1 1 0
M M L 2 9 2 _ f1 D o s e R e s p o n s e
lo g ([X ],M )
%Activity
IC50= 430µM
-5 .5 -5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
7 0
8 0
9 0
1 0 0
1 1 0
1 2 0
M M L 2 1 6 D o s e R e s p o n s e
lo g ([X ],M )
%Act.
IC50= 914.2µM
Assay Results
41. -5 .5 -5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
7 0
8 0
9 0
1 0 0
1 1 0
M M L 2 7 8 _ f2 D o s e R e s p o n s e
lo g ([X ],M )
%Act.
IC50= 1.904mM
-5 .0 -4 .5 -4 .0 -3 .5 -3 .0 -2 .5
6 0
7 0
8 0
9 0
1 0 0
1 1 0
1 2 0
M M L 3 1 6 _ f2 D o s e R e s p o n s e - T ria l II (4 -p t)
lo g ([X ],M )
%Act.
IC50=74.76µM
Assay Results
42. Formation of polycyclic structures
using olefin metathesis approach
M. F. El-Mansy , A. Sar , S. Chaudhury , N. J. Wallock and W. A. Donaldson , Org. Biomol. Chem.,
43. M. F. El-Mansy , A. Sar , S. Chaudhury , N. J. Wallock and W. A. Donaldson , Org. Biomol. Chem.,
44. Formation of polycyclic structures
using olefin metathesis approach
M. F. El-Mansy , A. Sar , S. Chaudhury , N. J. Wallock and W. A. Donaldson , Org. Biomol. Chem.,