Abbhi Vasudha, Saini Lovneet, Mishra Srishti, Sethi Gautam, Kumar Alan Prem, Piplani Poonam
University Institute of Pharmaceutical Sciences, UGC-Center of Advanced Study (UGC-CAS), Panjab University, Chandigarh 160014, India.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Bioorg Med Chem. 2017 Nov 1;25(21):6071-6085. doi: 10.1016/j.bmc.2017.09.045. Epub 2017 Oct 4.
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 IC 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.
Rho激酶抑制剂（ROCK II）因其降低眼压的能力和神经保护作用，在青光眼治疗中发挥着关键作用。在本研究中，合成了一系列新型苯并咪唑衍生物（9a - m），并对其降低眼压、抑制Rho激酶和抗氧化性能进行了评估。发现合成的化合物具有亲脂性，在治疗眼和对侧眼中均显示出显著的降低眼压效果，与参考标准法舒地尔相当。硝基苯基哌嗪取代的化合物9j在浓度为0.5和1 mM时分别表现出显著的降低眼压效果（51.56%），对ROCK II酶的抑制率分别为57.25%和77.92%。它具有相当强的自由基清除活性，在DPPH测定中IC值为95.49 μg/mL。化合物9j的分子对接研究表明该化合物在重组人ROCK II的活性位点结合，这使其成为一种有前景的抗青光眼药物。
