Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities

Yoon YK 1 , Ali MA 2 , Wei AC 3 , Choon TS 3 , Osman H 4 , Parang K 5 Show all authors , Shirazi AN 5

Affiliations 

  • 1 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. Electronic address: [email protected]
  • 2 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia; New Drug Discovery Research, Department of Medicinal Chemistry, Alwar Pharmacy College, Alwar 301030, Rajasthan, India; New Drug Discovery Research, Department of Medicinal Chemistry, Sunrise University, Alwar 301030, Rajasthan, India
  • 3 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
  • 4 School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia
  • 5 Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States
Bioorg Med Chem, 2014 Jan 15;22(2):703-10.
PMID: 24387981 DOI: 10.1016/j.bmc.2013.12.029

Abstract

A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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