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ID: ALA3593177

Journal: Bioorg Med Chem

Title: Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH.

Authors: Abdullah I, Chee CF, Lee YK, Thunuguntla SS, Satish Reddy K, Nellore K, Antony T, Verma J, Mun KW, Othman S, Subramanya H, Rahman NA.

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.

CiteXplore: 26088338

DOI: 10.1016/j.bmc.2015.05.051