In silico screening of drug Bank data base to PDE10: A drug repurposing approach

Abstract

Drug repurposing has emerged as a promising strategy for expediting drug development by identifying new therapeutic applications for existing drugs. In this study employed in silico screening approach to explore the DrugBank database for potential phosphodiesterase 10 (PDE10) inhibitors with applications in neurological, psychiatric disorders and cancer treatment. PDE10 plays a crucial role in regulating cyclic nucleotide levels in the brain and has been implicated in various diseases, including schizophrenia, Parkinson’s, Huntington’s diseases, and certain types of cancer. Through molecular docking, we evaluated the interactions and energetics of 28 candidate inhibitors with PDE10. Notably, 17 candidates met all selection criteria, presenting excellent potential for further investigation. The theoretical inhibitors demonstrated favorable ADMETx properties, and their adverse effects were comparable or lower than controls. These findings indicate the viability of repurposing existing drugs, such as Nebivolol, Fluvastatin, Pioglitazone and others, for PDE10 inhibition in diverse pathologies. Validation of these candidates in preclinical studies may open new avenues for drug development and clinical applications, addressing unmet medical needs in various disorders and cancer treatment.

Identification of Novel Quinolone and Quinazoline Alkaloids as Phosphodiesterase 10A Inhibitors for Parkinson’s Disease through a Computational Approach

“…Moreover, it formed a 6-ring pi–pi interaction involving the key residue, PHE729 (with a less negative docking score of −6.4385), at the distance and energy of 3.58 Å and −0.0 kcal/mol, respectively. While the hydrogen bond with accessible residues Ser677 and hydrophobic interaction with Ile692 may not significantly contribute to PDE10A inhibition (as they are not directly involved in cAMP/cGMP binding), similar interactions with these residues are evident in the profiles of reference PDE10 inhibitors like papaverine, Tofisopam, and Dipyridamole . Also, hydrophobic interaction with Ile692 plays a pivotal role in providing stability to the inhibitor in the PDE10A active site .…”