Unveiling of phosphodiesterase-5 hot residues binding to xanthine derivatives for erectile dysfunction therapy: A computational drug repurposing approach.

ABSTRACT: Overexpression of phosphodiesterase 5 (PDE-5) presents a compelling target for the therapy of erectile dysfunction. Sildenafil and other conventional PDE-5 inhibitors may lead to adverse effects, including visual disturbances and migraines. Therefore, the investigation of novel inhibitors with enhanced safety profiles is imperative. This research employed a computational drug repurposing approach to assess US-FDA-approved xanthine derivatives (XDs) for their efficacy in targeting PDE-5. XDs exhibit a favorable affinity for the active site of the PDE-5 receptor, with binding scores between -10.0 kcal/mol and -6.3 kcal/mol for linagliptin and theobromine, respectively. The top-ranked docked Xds then underwent 300-nanosecond molecular dynamics simulations. Linagliptin demonstrated greater sta

SUBMITTER: Elzupir AO 

PROVIDER: S-EPMC12614580 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature