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Your search keyword '"Magesh S"' showing total 3 results
Start Over Author "Magesh S" Publisher elsevier science ltd
3 results on '"Magesh S"'

1. Design and synthesis of novel iminothiazinylbutadienols and divinylpyrimidinethiones as ARE inducers.

Author

Chen L, Magesh S, Wang H, Yang CS, Kong AN, and Hu L

Subjects
Curcumin chemistry, Curcumin metabolism, Isothiocyanates chemistry, Isothiocyanates pharmacology, Molecular Structure, Pyrimidines chemical synthesis, Pyrimidines chemistry, Pyrimidines pharmacology, Structure-Activity Relationship, Sulfoxides, Thiadiazines chemical synthesis, Thiadiazines chemistry, Thiadiazines pharmacology, Thiones chemical synthesis, Thiones pharmacology, Thiourea chemistry, Thiourea metabolism, Antioxidant Response Elements drug effects, Drug Design, Thiones chemistry
Abstract

Novel iminothiazinylbutadienols and divinylpyrimidinethiones were designed and synthesized as analogues of curcumin with its diketone moiety masked as a heterocyclic adduct with thiourea. The chemical stability of these novel heterocyclic compounds was improved as compared to curcumin. They exhibit longer half-lives and do not react with nucleophilic thiols under physiological conditions. In an ARE-luciferase reporter assay, some of these new curcumin analogues are more effective ARE activators than curcumin and isothiocyanates., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
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2. Discovery of a small-molecule inhibitor and cellular probe of Keap1-Nrf2 protein-protein interaction.

Author

Hu L, Magesh S, Chen L, Wang L, Lewis TA, Chen Y, Khodier C, Inoyama D, Beamer LJ, Emge TJ, Shen J, Kerrigan JE, Kong AN, Dandapani S, Palmer M, Schreiber SL, and Munoz B

Subjects
Crystallography, X-Ray, Dose-Response Relationship, Drug, Fluorescence Polarization, High-Throughput Screening Assays, Humans, Isoquinolines chemistry, Kelch-Like ECH-Associated Protein 1, Models, Molecular, Molecular Probes chemistry, Molecular Structure, Phthalimides chemistry, Protein Binding drug effects, Small Molecule Libraries chemistry, Structure-Activity Relationship, Drug Discovery, Intracellular Signaling Peptides and Proteins metabolism, Isoquinolines pharmacology, Molecular Imaging, Molecular Probes pharmacology, NF-E2-Related Factor 2 metabolism, Phthalimides pharmacology, Small Molecule Libraries pharmacology
Abstract

A high-throughput screen (HTS) of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1-Nrf2 protein-protein interaction. The HTS hit has three chiral centers; a combination of flash and chiral chromatographic separation demonstrated that Keap1-binding activity resides predominantly in one stereoisomer (SRS)-5 designated as ML334 (LH601A), which is at least 100× more potent than the other stereoisomers. The stereochemistry of the four cis isomers was assigned using X-ray crystallography and confirmed using stereospecific synthesis. (SRS)-5 is functionally active in both an ARE gene reporter assay and an Nrf2 nuclear translocation assay. The stereospecific nature of binding between (SRS)-5 and Keap1 as well as the preliminary but tractable structure-activity relationships support its use as a lead for our ongoing optimization., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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3. Design, synthesis, and biological evaluation of human sialidase inhibitors. Part 1: selective inhibitors of lysosomal sialidase (NEU1).

Author

Magesh S, Moriya S, Suzuki T, Miyagi T, Ishida H, and Kiso M

Subjects
Drug Design, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Humans, Hydrogen Bonding, Models, Molecular, Molecular Structure, Enzyme Inhibitors chemistry, Lysosomes enzymology, Neuraminidase antagonists & inhibitors
Abstract

We here report the design and synthesis of selective human lysosomal sialidase (NEU1) inhibitors. A series of amide-linked C9 modified DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) analogues were synthesized and their inhibitory activities against all four human sialidases (NEU1-NEU4) were determined. Structure-based approach was used to investigate the basis of selectivity of the compounds with experimentally observed activity. Results from the present study are found to be informative in a qualitative manner for the further design of isoform selective human sialidase inhibitors for therapeutic value.

Published
2008
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