Combined High Throughput Screening with QSAR Analysis Unravel Potential Glyoxalase-I inhibitors

INTRODUCTION: Glyoxalase system is ubiquitous system in human cells which has been examined thoroughly for its role in cancerous diseases. It detoxifies endogenous harmful metabolites, mainly methylglyoxal (MG) into non-toxic bystanders. In previous work, our group has explored a series of compounds against glyoxalase I protein. METHOD: In this research, highthroughput screening approach was used to investigate the activity of in-house database composed of 205 compounds. RESULTS: 15 compounds were found active as glyoxalase I inhibitors. Structure based model Hypo(2ZA0_2_02) combined with 3D-QSAR modeling were applied to predict glyoxalase I inhibition and to explain their activity. The 15 candidates showed more than 50% inhibition with low micromolar IC50 ranges between 5.0 to 42.0 microM. CONCLUSION: The compounds have been successfully mapped and fitted the Hypo(2ZA0_2_02) model which explain the presence of anti-glyoxalase I activity. This model could be used in future for further development of new and novel glyoxylase I inhibitors.