Please use this identifier to cite or link to this item:
Title: Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition
Authors: Panathur, N.
Udayakumar, D.
Koushik, P.V.
Alvala, M.
Yogeeswari, P.
Sriram, D.
Kumar, V.
Issue Date: 2013
Citation: European Journal of Medicinal Chemistry, 2013, Vol.69, , pp.125-138
Abstract: In 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.
Appears in Collections:1. Journal Articles

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.