Panathur, N.Udayakumar, U.Koushik, P.V.Alvala, M.Yogeeswari, P.Sriram, D.Kumar, V.2026-02-052013European Journal of Medicinal Chemistry, 2013, 69, , pp. 125-1382235234https://doi.org/10.1016/j.ejmech.2013.08.018https://idr.nitk.ac.in/handle/123456789/26730In 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.1 [1 methyl 2 [4 phenyl 5 (propan 2 ylsulfanyl) 4h 1,2,4 triazol 3 yl] 1h indol 3 yl]methamine derivative2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 (morpholinomethyl) 1h indole2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(2 methylpiperidin 1 yl)methyl] 1h indole2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(3 methylpiperidin 1 yl)methyl] 1h indole2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(4 methylpiperidin 1 yl)methyl] 1h indole2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [[4 (pyrrolidin 1 yl)piperidine 1 yl]methyl] 1h indole3 [(2,6 dimethylmorpholino)methyl] 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indole5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 (morpholinomethyl) 1h indole5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 3 [(3 methylpiperidine 1 yl)methyl] 1h indoleantineoplastic agentcyclopropyl n[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1 1h indol 3 yl]methyl]methanaminecyclopropyl n[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl]methanamineindole derivativen[[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 aminen[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methly] 3 morpholinopropan 1 aminen[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl(4 methoxyphenyl)methanaminen[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 methoxyethan 1 aminen[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 morpholinoethan 1 aminen[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl](3 methoxyphenyl)methanaminen[[2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl]cyclopropanaminen[[2 [5 (isopropythio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 3,4,5 trimethoxybenzenaminen[[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 aminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 methoxyethan 1 aminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 2 morpholinoethan 1 aminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 3 morpholinopropan 1 aminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl] 3,4,5 trimethoxybenzenaminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl](3 methoxyphenyl)methanaminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl](4 methoxyphenyl)methanaminen[[5 fluoro 2 [5 (isopropylthio) 4 phenyl 4h 1,2,4 triazol 3 yl] 1 methyl 1h indol 3 yl]methyl]cyclopropanamineunclassified drugunindexed druganimal experimentanimal modelantineoplastic activityarticlebody weightcancer cell culturecancer inhibitioncontrolled studycytotoxicitydeacetylationdrug synthesishumanhuman cellin vitro studyin vivo studymalemolecular dockingmolecular interactionnonhumanprostate hypertrophyprostate weightratBreast cancerHuman SIRT1IndoleLeukemiaProstate hyperplasiaAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHEK293 CellsHistone Deacetylase InhibitorsHumansHyperplasiaIndolesK562 CellsMaleModels, MolecularMolecular StructureRatsRats, WistarSirtuin 1Small Molecule LibrariesStructure-Activity RelationshipTestosterone