Rational Design of New Phosphodiesterase Inhibitors: An In Silico Approach Oriented Toward Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide and, due
to the limited efficacy of current treatments, phosphodiesterase (PDE) has emerged as a
promising new therapeutic target. In this context, this study proposed the development
of two novel PDE inhibitors using in silico approaches. Docking results revealed high
binding affinities and effective enzyme inhibition. Recurring interactions with residues
in the PDE active site suggest a stable inhibition mechanism, reinforcing the potential
of the designed compounds as promising candidates for AD treatment, while also
providing valuable insights for the rational development of new therapeutic agents