Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles
Document Type
Article
Publication Date
1-1-2017
Abstract
Both sirtuin and poly(ADP-ribose)polymerase (PARP) family of enzymes utilize NAD+ as co-substrate. Inhibitors of sirtuins and PARPs are important tools in drug discovery as they are reported to be linked to multiple diseases such as cancer. New potent sirtuin inhibitors (2,4,6-trisubstituted benzimidazole) were discovered from reported PARP inhibitor scaffold. Interestingly, the synthesized compounds have contrasting sirtuin and PARP-1 inhibitory activities. We showed that modification on benzimidazoles may alter their selectivity toward sirtuin or PARP-1 enzymes. This offers an opportunity for further discovery and development of new promising sirtuin inhibitors. Molecular docking studies were carried out to aid the rationalization of these observations. Preliminary antiproliferative studies of selected compounds against nasopharyngeal cancer cells also showed relatively promising results.
Keywords
anticancer, benzimidazole, molecular docking, nasopharyngeal, poly(ADP-ribose) polymerases, sirtuin
Divisions
CHEMISTRY
Funders
Monash University Malaysia SEED Fund,RUC Research Grant (1001/PSK/8620012)
Publication Title
Chemical Biology & Drug Design
Volume
91
Issue
1
Publisher
Wiley