Hunig's base catalyzed synthesis of new 1-(2,3-dihydro-1H-inden-1-yl)-3-aryl urea/thiourea derivatives as potent antioxidants and 2HCK enzyme growth inhibitors

Autor: Swetha Vallela, Visweswara Rao Pasupuleti, Grigoriy V. Zyryanov, Venkataramana Lachhi Reddy, Naga Raju Chamarthi, Jaya Shree Anireddy, Vijay Kumar Reddy Avula
Rok vydání: 2019
Předmět:
PHYSICAL CHEMISTRY
Antioxidant
medicine.medical_treatment
IC50
01 natural sciences
Biochemistry
Antioxidants
PROTEIN TYROSINE KINASE
CELL NUCLEUS RECEPTOR
CHEMISTRY
ANTIOXIDANT
DRUG ABSORPTION
ELEMENTAL ANALYSIS
Drug Discovery
HUMAN CELL
Urea
chemistry.chemical_classification
HUMAN
THIOUREA DERIVATIVE
DRUG DISTRIBUTION
QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP
LIGANDS
PROTEIN KINASE INHIBITORS
IN VITRO STUDY
PROTEIN-TYROSINE KINASES
Stereochemistry
Radical
UREA/THIO-UREA DERIVATIVE
CARBON NUCLEAR MAGNETIC RESONANCE
Residue (chemistry)
QUANTITATIVE STRUCTURE ACTIVITY RELATION
MDCK CELL LINE
2
3-DIHYDRO-1H-INDEN-1-AMINE
NONHUMAN
Humans
FREE RADICAL
CACO-2 CELL LINE
DRUG METABOLISM
Molecular Biology
010405 organic chemistry
CATALYSIS
0104 chemical sciences
1
1 DIPHENYL 2 PICRYLHYDRAZYL
PROTON NUCLEAR MAGNETIC RESONANCE
chemistry
CACO-2 CELLS
THIOUREA
MOLECULAR DOCKING STUDIES
NEUROPROTECTIVE AGENT
BLOOD-BRAIN BARRIER
DRUG EXCRETION
ELECTROSPRAY MASS SPECTROMETRY
MOLECULAR DOCKING SIMULATION
Quantitative Structure-Activity Relationship
UNCLASSIFIED DRUG
Ligands
chemistry.chemical_compound
PROTEIN KINASE INHIBITOR
ANTIOXIDANTS
MOLECULAR DOCKING
1 (2
3 DIHYDRO 1H INDEN 1 YL) 3 (4 FLUOROPHENYL)UREA
PRIORITY JOURNAL
2HCK ENZYME GROWTH INHIBITION
CATALYST
Hydrogen bond
Thiourea
HUMANS
Protein-Tyrosine Kinases
Molecular Docking Simulation
NEUROPROTECTIVE AGENTS
Neuroprotective Agents
BLOOD BRAIN BARRIER
Blood-Brain Barrier
ASCORBIC ACID
NUCLEOPHILICITY
PHOSPHOTRANSFERASE INHIBITOR
ADMET PROPERTIES
PLASMA PROTEIN BINDING
Catalysis
medicine
ARTICLE
Protein Kinase Inhibitors
Aryl
DRUG SYNTHESIS
Organic Chemistry
PROTEIN TYROSINE KINASE INHIBITOR
UREA DERIVATIVE
ULTRAVIOLET RADIATION
CONTROLLED STUDY
010404 medicinal & biomolecular chemistry
Enzyme
ANIMAL CELL
CELL PROLIFERATION
THIN LAYER CHROMATOGRAPHY
LIGAND
UREA
Caco-2 Cells
PROTEINASE INHIBITOR
ANTIOXIDANT ACTIVITY
Zdroj: Bioorg. Chem.
Bioorganic Chemistry
ISSN: 1090-2120
Popis: A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h & 4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo. © 2019 Elsevier Inc. One of the authors Dr. Avula Vijay Kumar Reddy is thankful to Ural Federal University, Yekaterinburg, Russian Federation for providing Postdoctoral Fellowship.
Databáze: OpenAIRE
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