Computational Screening of Bioactive Compounds of Gymnema sylvestre for ALR2 Inhibition: A Virtual Screening Approach

Background/Objectives: Complications associated with diabetes are predominantly influenced by the polyol pathway, in which aldose reductase 2 (ALR2) is instrumental in converting surplus glucose into sorbitol, resulting in oxidative stress and cellular injury. Targeting ALR2 with natural inhibitors offers a promising therapeutic approach. Materials and Methods: This study utilized molecular docking-based virtual screening and screened 182 bioactive compounds from Gymnema sylvestre (GS) against ALR2. The co-crystallized ligand (IDD594) served as a benchmark for comparison. The co-crystallized ligand (IDD594) was utilized as a positive control. Additional molecular descriptors and drug-likeness evaluations were conducted utilizing the local online traditional use system (LOTUS) database. Results: Among the screened compounds, LTS0010237, LTS0042292, and LTS0072617 demonstrated superior binding affinities compared to the control, engaging with critical ALR2 residues. The analyses demonstrated advantageous lipophilicity, solubility, and structural stability. The top three compounds complied with Lipinski’s Rule of Five (RO5), indicating favorable pharmacokinetic characteristics. Conclusion: The results underscore the therapeutic potential of compounds derived from GS as ALR2 inhibitors, necessitating further validation to evaluate their effectiveness in alleviating diabetes-related complications.