Journal of Diabetes & Metabolism

ISSN - 2155-6156

IDesign of novel rho kinase inhibitors for the treatment of diabetic complications using energy based pharmacophore modeling, in-silico screening and docking studies

3rd World Congress on Diabetes & Metabolism

September 24-26, 2012 Marriott Convention Center, Hyderabad, India

Ram Kumar Mishra, Reshma Chowdary, D. Sriram and P. Yogeeswari

Posters: J Diabetes Metab

Abstract :

Rho kinase (ROCK) is a serine/threonine kinase, which is activated by binding with the activated form of a low molecular weight G protein, Rho. ROCK plays important roles in a variety of cellular functions such as cell motility, smooth muscle contraction and cytoskeletal reorganisation of non-muscle cells. ROCK inhibitors have been considered to be a target for potential treatment of diabetic complications like diabetic neuropathy, nephropathy, erectile dysfunction, hypertension, retinopathy and injury caused by ischaemia and reperfusion. A number of synthetic inhibitors of the ROCK have been developed recently. In this study, energy-based pharmacophore model and molecular docking approach were used to characterize the binding features of three different Rho kinase (ROCK) inhibitors. The energy based pharmacophores were generated using E-pharmacophore module of Schrodinger suit of softwares. The pharmacophore models thus generated had acceptor and aromatic feature and a presence of aryl ring system seemed to be essential for inhibitors in term of their binding affinities. The energy based pharmacophores were then used for virtual screening and the top hits were docked. Here, on the basis of pharmacophore modelling, virtual screening and molecular docking studies, we report possible pharmacophores and a series of ROCK inhibitors which might be valuable for designing new ROCK inhibitors.