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Title: Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH
Authors: Abdullah, I. 
Chee, C.F. 
Lee, Y.-K. 
Thunuguntla, S.S.R. 
Satish Reddy, K. 
Nellore, K. 
Antony, T. 
Verma, J. 
Mun, K.W. 
Othman, S. 
Subramanya, H. 
Rahman, N.A. 
Issue Date: 2015
Journal: Bioorganic and Medicinal Chemistry Volume 23, Issue 15, 23 July 2015, Pages 4669-4680 
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. © 2015 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.bmc.2015.05.051
Appears in Collections:COE Scholarly Publication

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