Jump to main content
Jump to site search

Issue 2, 2015
Previous Article Next Article

Decorated 6,6′,7,7′-tetrahydro-1H,1′H-2,3′-biindole scaffold as promising candidate for recognition of the CDK2 allosteric site

Author affiliations

Abstract

Progression through the S phase of the cell cycle is controlled by cyclin-dependent kinase 2 (CDK2), the activity of which depends on its binding to regulatory partners (cyclins E and A). Deregulation of the activity of CDK2 has been associated with several types of sickness, such as infectious, neurodegenerative, and proliferative diseases. Based on these data, CDK2 has become an attractive target for the development of new anticancer drugs. Indoledione derivatives have recently received special attention in virtue of their pronounced biological effects, such as antiproliferative, antioxidant and antimicrobial properties. In the present work we have investigated the antiproliferative effect of an indolone-based derivative, namely DPIT, whose synthesis we have recently reported, with the aim to clarify its mechanism of action. Furthermore, docking studies have been performed on the eight stereoisomers of DPIT to investigate their capacity to interact as a ligand with ortho- or allosteric sites of CDK2. The encouraging results showed DPIT as a promising candidate for a new type 3 class of inhibitors of CDK2 that recognize the allosteric site.

Graphical abstract: Decorated 6,6′,7,7′-tetrahydro-1H,1′H-2,3′-biindole scaffold as promising candidate for recognition of the CDK2 allosteric site

Back to tab navigation

Publication details

The article was received on 19 Aug 2014, accepted on 31 Oct 2014 and first published on 03 Nov 2014


Article type: Concise Article
DOI: 10.1039/C4MD00364K
Author version
available:
Download author version (PDF)
Med. Chem. Commun., 2015,6, 311-318

  •   Request permissions

    Decorated 6,6′,7,7′-tetrahydro-1H,1′H-2,3′-biindole scaffold as promising candidate for recognition of the CDK2 allosteric site

    A. Rescifina, A. Scala, M. T. Sciortino, I. Colao, G. Siracusano, A. Mazzaglia, U. Chiacchio and G. Grassi, Med. Chem. Commun., 2015, 6, 311
    DOI: 10.1039/C4MD00364K

Search articles by author

Spotlight

Advertisements