Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition

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dc.contributor.authorPanathur, N.
dc.contributor.authorUdayakumar, U.
dc.contributor.authorKoushik, P.V.
dc.contributor.authorAlvala, M.
dc.contributor.authorYogeeswari, P.
dc.contributor.authorSriram, D.
dc.contributor.authorKumar, V.
dc.date.accessioned2026-02-05T09:34:41Z
dc.date.issued2013
dc.description.abstractIn our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-[4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3- yl]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia. © 2013 Elsevier Masson SAS. All rights reserved.
dc.identifier.citationEuropean Journal of Medicinal Chemistry, 2013, 69, , pp. 125-138
dc.identifier.issn2235234
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2013.08.018
dc.identifier.urihttps://idr.nitk.ac.in/handle/123456789/26730
dc.subject1 [1 methyl 2 [4 phenyl 5 (propan 2 ylsulfanyl) 4h 1,2,4 triazol 3 yl] 1h indol 3 yl]methamine derivative
dc.subject2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 (morpholinomethyl) 1h indole
dc.subject2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(2 methylpiperidin 1 yl)methyl] 1h indole
dc.subject2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(3 methylpiperidin 1 yl)methyl] 1h indole
dc.subject2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(4 methylpiperidin 1 yl)methyl] 1h indole
dc.subject2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [[4 (pyrrolidin 1 yl)piperidine 1 yl]methyl] 1h indole
dc.subject3 [(2,6 dimethylmorpholino)methyl] 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indole
dc.subject5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 (morpholinomethyl) 1h indole
dc.subject5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(3 methylpiperidine 1 yl)methyl] 1h indole
dc.subjectantineoplastic agent
dc.subjectcyclopropyl n[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1 1h indol 3 yl]methyl]methanamine
dc.subjectcyclopropyl n[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl]methanamine
dc.subjectindole derivative
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 (pyrrolidin 1 yl)ethan 1 amine
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methly] 3 morpholinopropan 1 amine
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl(4 methoxyphenyl)methanamine
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 methoxyethan 1 amine
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 morpholinoethan 1 amine
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl](3 methoxyphenyl)methanamine
dc.subjectn[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl]cyclopropanamine
dc.subjectn[[2 [5 (isopropythio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 3,4,5 trimethoxybenzenamine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 9pyrrolidin 1 yl)ethan 1 amine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 methoxyethan 1 amine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 morpholinoethan 1 amine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 3 morpholinopropan 1 amine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 3,4,5 trimethoxybenzenamine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl](3 methoxyphenyl)methanamine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl](4 methoxyphenyl)methanamine
dc.subjectn[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl]cyclopropanamine
dc.subjectunclassified drug
dc.subjectunindexed drug
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectantineoplastic activity
dc.subjectarticle
dc.subjectbody weight
dc.subjectcancer cell culture
dc.subjectcancer inhibition
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectdeacetylation
dc.subjectdrug synthesis
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectmale
dc.subjectmolecular docking
dc.subjectmolecular interaction
dc.subjectnonhuman
dc.subjectprostate hypertrophy
dc.subjectprostate weight
dc.subjectrat
dc.subjectBreast cancer
dc.subjectHuman SIRT1
dc.subjectIndole
dc.subjectLeukemia
dc.subjectProstate hyperplasia
dc.subjectAnimals
dc.subjectAntineoplastic Agents
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectDose-Response Relationship, Drug
dc.subjectDrug Screening Assays, Antitumor
dc.subjectHEK293 Cells
dc.subjectHistone Deacetylase Inhibitors
dc.subjectHumans
dc.subjectHyperplasia
dc.subjectIndoles
dc.subjectK562 Cells
dc.subjectMale
dc.subjectModels, Molecular
dc.subjectMolecular Structure
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectSirtuin 1
dc.subjectSmall Molecule Libraries
dc.subjectStructure-Activity Relationship
dc.subjectTestosterone
dc.titleIdentification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition

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