Combined High Throughput Screening with QSAR Analysis Unravelling Potential Glyoxalase-I Inhibitors.

AIMS: Discovery of new Glo-I inhibitors as potential anticancer agents.

BACKGROUND

Glyoxalase system is ubiquitous system in human cells which has been examined thoroughly for its role in cancerous diseases. It performs detoxifying endogenous harmful metabolites, mainly methylglyoxal (MG) into non-toxic bystanders.

OBJECTIVE

Structure based model Hypo(2ZA0_2_02) combined with 3D-QSAR modeling were applied to predict glyoxalase I inhibition and to explain their activity.

METHODS

Currently, high throughput screening approach was used to investigate the activity of inhouse database composed of 205 compounds.

RESULTS

15 compounds were found active as glyoxalase I inhibitors. The 15 candidates showed more than 50% inhibition with low micromolar IC50 ranges between 5.0 to 42.0 μM.

CONCLUSION

They 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.