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

Panathur, Naveen and Dalimba, Udaya Kumar and Koushik, Pulla Venkat and Alvala, Mallika and Yogeeswari, Perumal and Sriram, Dharmarajan and Kumar, V (2013) Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition. In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 69 . pp. 125-138.

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Official URL: http://dx.doi.org/10.1016/j.ejmech.2013.08.018


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. (C) 2013 Elsevier Masson SAS. All rights reserved.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to the ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, FRANCE
Keywords: Indole; Leukemia; Breast cancer; Prostate hyperplasia; Human SIRT1
Department/Centre: Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Depositing User: Id for Latest eprints
Date Deposited: 07 Mar 2014 07:43
Last Modified: 05 Mar 2019 05:33
URI: http://eprints.iisc.ac.in/id/eprint/48509

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