Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/101611
Title: 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
Authors: Lachhi, Reddy, V.
Avula, V. K. R.
Zyryanov, G. V.
Vallela, S.
Anireddy, J. S.
Pasupuleti, V. R.
Chamarthi, N. R.
Зырянов, Г. В.
Issue Date: 2020
Publisher: Academic Press Inc.
Citation: 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 / V. Lachhi Reddy, V. K. R. Avula, G. V. Zyryanov, et al. — DOI 10.1016/j.bioorg.2019.103558 // Bioorganic Chemistry. — 2020. — Vol. 95. — 103558.
Abstract: 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.
Keywords: 2,3-DIHYDRO-1H-INDEN-1-AMINE
2HCK ENZYME GROWTH INHIBITION
ADMET PROPERTIES
ANTIOXIDANT ACTIVITY
MOLECULAR DOCKING STUDIES
UREA/THIO-UREA DERIVATIVE
1 (2,3 DIHYDRO 1H INDEN 1 YL) 3 (4 FLUOROPHENYL)UREA
1,1 DIPHENYL 2 PICRYLHYDRAZYL
ANTIOXIDANT
ASCORBIC ACID
CELL NUCLEUS RECEPTOR
FREE RADICAL
PHOSPHOTRANSFERASE INHIBITOR
PROTEIN TYROSINE KINASE INHIBITOR
PROTEINASE INHIBITOR
THIOUREA DERIVATIVE
UNCLASSIFIED DRUG
UREA DERIVATIVE
ANTIOXIDANT
LIGAND
NEUROPROTECTIVE AGENT
PROTEIN KINASE INHIBITOR
PROTEIN TYROSINE KINASE
THIOUREA
UREA
ANIMAL CELL
ANTIOXIDANT ACTIVITY
ARTICLE
BLOOD BRAIN BARRIER
CACO-2 CELL LINE
CARBON NUCLEAR MAGNETIC RESONANCE
CATALYST
CELL PROLIFERATION
CONTROLLED STUDY
DRUG ABSORPTION
DRUG DISTRIBUTION
DRUG EXCRETION
DRUG METABOLISM
DRUG SYNTHESIS
ELECTROSPRAY MASS SPECTROMETRY
ELEMENTAL ANALYSIS
HUMAN
HUMAN CELL
IC50
IN VITRO STUDY
MDCK CELL LINE
MOLECULAR DOCKING
NONHUMAN
NUCLEOPHILICITY
PHYSICAL CHEMISTRY
PLASMA PROTEIN BINDING
PRIORITY JOURNAL
PROTON NUCLEAR MAGNETIC RESONANCE
QUANTITATIVE STRUCTURE ACTIVITY RELATION
THIN LAYER CHROMATOGRAPHY
ULTRAVIOLET RADIATION
CATALYSIS
CHEMISTRY
ANTIOXIDANTS
BLOOD-BRAIN BARRIER
CACO-2 CELLS
CATALYSIS
HUMANS
LIGANDS
MOLECULAR DOCKING SIMULATION
NEUROPROTECTIVE AGENTS
PROTEIN KINASE INHIBITORS
PROTEIN-TYROSINE KINASES
QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP
THIOUREA
UREA
URI: http://hdl.handle.net/10995/101611
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85077326480
PURE ID: 11727012
b9feee79-6f52-48b5-9e7a-deed901a15f1
ISSN: 452068
DOI: 10.1016/j.bioorg.2019.103558
metadata.dc.description.sponsorship: One of the authors Dr. Avula Vijay Kumar Reddy is thankful to Ural Federal University, Yekaterinburg, Russian Federation for providing Postdoctoral Fellowship.
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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