Drug repurposing against galectin-3 using simulation-based studies.

Area of Science:

• Biochemistry
• Computational Biology
• Pharmacology

Background:

• Galectin, a carbohydrate-binding protein, plays roles in cell proliferation, inflammation, and apoptosis.
• Galectin-3 is a stable biomarker with altered expression in various diseases, making it a potential therapeutic target.
• Cardiovascular medications are explored for novel therapeutic applications beyond their primary indications.

Purpose of the Study:

• To computationally screen cardiovascular medications for their potential to inhibit Galectin-3 biological activities.
• To identify specific compounds with high binding affinity to Galectin-3 using bioinformatics techniques.
• To lay the groundwork for experimental validation of identified drug candidates.

Main Methods:

• A computational pipeline combining unsupervised clustering, molecular docking, and molecular dynamics (MD) simulations was developed.
• Virtual screening of a chemical library was performed to prioritize potential Galectin-3 inhibitors.
• Clustering utilized gene expression, mode of action, and chemical descriptors for molecule prioritization.

Main Results:

• Twenty-four compounds were screened and repurposed against Galectin-3.
• Molecular docking identified Bufalin, Cymarin, and Ouabalin exhibiting high binding affinities due to polar interactions with key amino acid residues (Arg144, Glu184, Arg162, His158, Asn174).
• MD simulations corroborated the inhibitory potential of the identified compounds against Galectin-3.

Conclusions:

• Bufalin, Cymarin, and Ouabalin demonstrate significant potential as Galectin-3 inhibitors based on computational analysis.
• Further experimental and in vivo validation studies are warranted to confirm the therapeutic efficacy of these repurposed cardiovascular drugs.
• This study highlights the utility of bioinformatics in drug repurposing for novel therapeutic targets like Galectin-3.