Contrasting sirtuin and poly(ADP-ribose)polymerase activities of selected 2,4,6-trisubstituted benzimidazoles

Keng Yoon Yeong, Soo Choon Tan, Chun Wai Mai, Chee Onn Leong, Felicia Fei Lei Chung, Yean Kee Lee, Chin Fei Chee, Noorsaadah Abdul Rahman

    Research output: Contribution to journalArticleResearchpeer-review

    14 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)213-219
    Number of pages7
    JournalChemical Biology & Drug Design
    Volume91
    Issue number1
    DOIs
    Publication statusPublished - Jan 2018

    Keywords

    • anticancer
    • benzimidazole
    • molecular docking
    • nasopharyngeal
    • poly(ADP-ribose) polymerases
    • sirtuin

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