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


Autoria(s): Panathur, Naveen; Dalimba, Udayakumar; Koushik, Pulla Venkat; Alvala, Mallika; Yogeeswari, Perumal; Sriram, Dharmarajan; Kumar, V
Data(s)

2013

Resumo

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.

Formato

application/pdf

Identificador

http://eprints.iisc.ernet.in/48509/1/eur_jou_69_123_2013.pdf

Panathur, Naveen and Dalimba, Udayakumar 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.

Publicador

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Relação

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

http://eprints.iisc.ernet.in/48509/

Palavras-Chave #Solid State & Structural Chemistry Unit
Tipo

Journal Article

PeerReviewed