Affiliations 

  • 1 Drug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, Malaysia. Electronic address: Iskandar.a@um.edu.my
  • 2 Drug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, Malaysia; Aurigene Discovery Technologies (Malaysia) Sdn. Bhd, Malaysia; School of Pharmacy, International Medical University, 57000 Kuala Lumpur, Malaysia
  • 3 Drug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, Malaysia
  • 4 Aurigene Discovery Technologies (India) Ltd, India
  • 5 Aurigene Discovery Technologies (Malaysia) Sdn. Bhd, Malaysia
  • 6 Drug Design and Development Research Group, Department of Chemistry, Faculty of Science, University of Malaya, Malaysia; Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Malaysia
Bioorg Med Chem, 2015 Aug 01;23(15):4669-4680.
PMID: 26088338 DOI: 10.1016/j.bmc.2015.05.051

Abstract

Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design. Since these enzymes share a common role in the DNA replication and repair mechanisms, it may be beneficial to target both PARP-1 and DHODH in attempts to design new anti-cancer agents. Benzimidazole derivatives have shown a wide variety of pharmacological activities including PARP and DHODH inhibition. We hereby report the design, synthesis and bioactivities of a series of benzimidazole derivatives as inhibitors of both the PARP-1 and DHODH enzymes.

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