Virtual screening of RAGE inhibitors using molecular docking.

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Advanced Glycation End products (AGEs) trigger inflammatory responses in vascular cells via the Receptor for AGEs (RAGE).
• Targeting the RAGE pathway is crucial for managing vascular complications, including diabetic retinopathy.

Purpose of the Study:

• To design and identify novel RAGE inhibitors.
• To explore potential therapeutic agents for diabetic retinopathy and associated vascular issues.

Main Methods:

• A library of 352 compounds, based on Isoflavone and Argpyrimidine, was synthesized.
• Molecular docking simulations were performed using MolDock against the RAGE structure (PDB ID: 3CJJ).
• Compound 62 was evaluated for its ADME properties and toxicity profile.

Main Results:

• Compound 62 demonstrated favorable ADME properties and no predicted toxicity.
• Compound 62 exhibited significant binding affinity to RAGE, indicating its potential as an inhibitor.
• The identified compound possesses key pharmacophore features essential for RAGE inhibition.

Conclusions:

• Compound 62 is a promising RAGE inhibitor candidate.
• Further validation of compound 62 is warranted for the treatment of diabetic retinopathy and vascular complications.