Natural phosphodiesterase 5 (PDE5) inhibitors: a computational approach

In 1998, sildenafil was marketed as the first FDA-approved oral drug for the treatment of erectile dysfunction (ED). During the last two decades, the commercialization of other synthetic phosphodiesterase 5 (PDE5) inhibitors has been paralleled by the rise of remedies based on natural molecules from different chemical classes (flavonoids, polyphenols and alkaloids in general). In this work, a set of in silico tools were applied to study a panel of 30 natural compounds claimed to be effective against ED in the scientific literature or in folk medicine. First, pharmacokinetic properties were analysed to exclude the compounds lacking in specific drug-like features. Estimated binding energy for PDE5 and selectivity towards other PDE isoforms were then considered to highlight some promising molecules. Finally, a detailed structural investigation of the interaction pattern with PDE in comparison with sildenafil was conducted for the best performing compound of the set.

Automated summary

In 1998, sildenafil was introduced as the first FDA-approved oral drug for treating erectile dysfunction (ED). Over the past two decades, the development of other synthetic PDE5 inhibitors has been accompanied by the increasing popularity of natural remedies from various chemical classes. In this study, in silico tools were used to evaluate the efficacy of 30 natural compounds claimed to be effective against ED, focusing on pharmacokinetic properties, binding energies for PDE5, and comparison with sildenafil's interaction pattern with PDE.