Design and Synthesis of Benzimidazole-based Rho Kinase inhibitors for the treatment of Glaucoma

Publication date: Available online 4 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Vasudha Abbhi, Lovneet Saini, Srishti Mishra, Gautam Sethi, Alan Prem Kumar, Poonam Piplani
Rho kinase inhibitors (ROCK II) play a key role in glaucoma management attributed to their IOP lowering ability and neuroprotective effects. In the present study, a series of novel benzimidazole derivatives (9a-m) has been synthesized and evaluated for their IOP lowering, Rho kinase inhibitory and antioxidant properties. The synthesized compounds were found to be lipophilic and showed a significant IOP lowering effect both in the treated and the contralateral eye comparable to the reference standard fasudil. The nitrophenyl piperazine substituted compound 9j exhibited significant IOP lowering (51.56%) and an inhibition of 57.25 and 77.92% towards ROCK II enzyme at a concentration of 0.5 and 1 mM respectively. It possessed a considerable free radical scavenging activity exhibiting an IC50 value of 95.49 µg/mL in DPPH assay. The molecular docking studies of compound 9j indicated the binding of the compound at the active site of recombinant human ROCK II which makes it a promising antiglaucoma agent.

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