New indole-isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies
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Date
2015
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier Ltd
Abstract
A new series of indole-isoxazolone hybrids bearing substituted amide, substituted [(1,2,3-triazol-4-yl)methoxy]methyl group or substituted benzylic ether at position-2 of the indole nucleus was synthesised using a facile synthetic route and the molecules were characterised using spectroscopic techniques. The molecules were screened against three human cancer cell lines to evaluate their in vitro cytotoxic property. Most of the trifluoromethyl substituted derivatives exhibited better growth inhibition activity than their methyl substituted analogues. The SIRT1 inhibition activity of two potent molecules (I17 and I18) was investigated and the SIRT1 IC<inf>50</inf> values are 35.25 and 37.36 ?M, respectively for I17 and I18. The molecular docking studies with SIRT1 enzyme revealed favourable interactions of the molecule I17 with the amino acids constituting the receptor enzyme. © 2015 Elsevier Ltd. All rights reserved.
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Keywords
3 methyl 4 [(1 methyl 1h indol 3 yl)methylene]isoxazolone 5 one derivative, 4 [[2 (benzyloxymethyl) 5 fluoro 1 methyl 1h indol 3 yl]methylene] 3 methyl isoxazol 5 (4h) one, 4 [[2 [[(1 benzyl 1h 1,2,3 triazol 4 yl)methoxy]methyl] 5 fluoro 1 methyl 1h indol 3 yl]methtylene] 3 methylisoxazol 5 one, amide, antineoplastic agent, aspartic acid, glutamine, indole derivative, isoleucine, isoxazole derivative, sirtuin 1, unclassified drug, histone deacetylase inhibitor, indole, protein binding, antineoplastic activity, Article, breast metastasis, cancer cell line, cancer inhibition, chemical analysis, chemical reaction, clinical evaluation, controlled study, cytotoxicity, drug structure, drug synthesis, enzyme inhibition, growth inhibition, HT 29 cell line, human, human cell, IC50, in vitro study, MCF 7 cell line, metabolic stability, molecular docking, pharmacophore, protein interaction, reaction analysis, antagonists and inhibitors, binding site, cell proliferation, chemistry, drug effects, enzyme active site, HEK293 cell line, metabolism, structure activity relation, synthesis, tumor cell line, Binding Sites, Catalytic Domain, Cell Line, Tumor, Cell Proliferation, HEK293 Cells, Histone Deacetylase Inhibitors, Humans, Indoles, Isoxazoles, Molecular Docking Simulation, Protein Binding, Sirtuin 1, Structure-Activity Relationship
Citation
Bioorganic and Medicinal Chemistry Letters, 2015, 25, 14, pp. 2768-2772