Title:Combined High Throughput Screening with QSAR Analysis Unravelling Potential Glyoxalase-I Inhibitors
VOLUME: 16 ISSUE: 6
Author(s):Mahmoud A. Al-Sha’er*, Qosay A. Al-Balas and Mohammad A. Hassan
Affiliation:Faculty of Pharmacy, Zarqa University, Zarqa 13132, Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid
Keywords:Human glyoxalase-I, metalloenzyme, anticancer, zinc-binding groups, methylglyoxal (MG), QSAR.
Abstract:
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.
