Panathur, N.Gokhale, N.Udayakumar, U.Koushik, P.V.Yogeeswari, P.Sriram, D.2026-02-052015Bioorganic and Medicinal Chemistry Letters, 2015, 25, 14, pp. 2768-27720960894Xhttps://doi.org/10.1016/j.bmcl.2015.05.015https://idr.nitk.ac.in/handle/123456789/26279A 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.3 methyl 4 [(1 methyl 1h indol 3 yl)methylene]isoxazolone 5 one derivative4 [[2 (benzyloxymethyl) 5 fluoro 1 methyl 1h indol 3 yl]methylene] 3 methyl isoxazol 5 (4h) one4 [[2 [[(1 benzyl 1h 1,2,3 triazol 4 yl)methoxy]methyl] 5 fluoro 1 methyl 1h indol 3 yl]methtylene] 3 methylisoxazol 5 oneamideantineoplastic agentaspartic acidglutamineindole derivativeisoleucineisoxazole derivativesirtuin 1unclassified drughistone deacetylase inhibitorindoleprotein bindingantineoplastic activityArticlebreast metastasiscancer cell linecancer inhibitionchemical analysischemical reactionclinical evaluationcontrolled studycytotoxicitydrug structuredrug synthesisenzyme inhibitiongrowth inhibitionHT 29 cell linehumanhuman cellIC50in vitro studyMCF 7 cell linemetabolic stabilitymolecular dockingpharmacophoreprotein interactionreaction analysisantagonists and inhibitorsbinding sitecell proliferationchemistrydrug effectsenzyme active siteHEK293 cell linemetabolismstructure activity relationsynthesistumor cell lineBinding SitesCatalytic DomainCell Line, TumorCell ProliferationHEK293 CellsHistone Deacetylase InhibitorsHumansIndolesIsoxazolesMolecular Docking SimulationProtein BindingSirtuin 1Structure-Activity Relationship