Title:A Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening
Volume: 21
Issue: 16
Author(s): Abhijit Debnath, Hema Chaudhary*, Parul Sharma, Rajesh Singh and Shikha Srivastava
Affiliation:
- School of Medical and Allied Sciences, K.R. Mangalam University,
Sohna Road, Gurugram, India
Keywords:
PDE5, PDE5 inhibitors, erectile dysfunction, pulmonary arterial hypertension, benign prostatic hyperplasia, ADME profile.
Abstract:
Background: PDE5 inhibitors have had a surge in popularity over the last decade owing
to their efficacy in the treatment of erectile dysfunction, coronary vasculopathy, and pulmonary arterial
hypertension. These inhibitors exhibit competitive binding with phosphodiesterase type 5 and
inhibit the hydrolysis of cyclic guanosine monophosphate, hence elevating the levels of cGMP in
smooth muscle cells and prolonging the duration of an erection. However, due to production costs
and side effects, further research is needed to discover new PDE5 inhibitors.
Objectives: The study aimed to identify potent PDE5 inhibitors by employing the extensive application
of computer-aided drug design.
Methods: Three different databases, named Million Molecules Database, Natural Product Database,
and NCI Database, have been screened, which has been followed by filtering based on various druglikeness
rules, docking, ADME, toxicity, consensus molecular docking, and 100 ns molecular dynamics
simulation.
Results: Three compounds (ZINC05351336, ZINC12030898, and ZINC17949426) have exhibited
stable-binding characteristics at the active site of PDE5, demonstrating a robust binding affinity.
These molecules have been found to possess drug-like capabilities, effective ADME features, low
toxicity, and high stability.
Conclusion: The study has delved into the realm of PDE5 inhibitors, which have been found to be
effective in treating erectile dysfunction, but high production costs and side effects necessitate new
ones. Through computer-aided drug design and screening, three compounds have been identified
with promising binding characteristics, drug-appropriate properties, effective ADME profiles, minimal
toxicity, and stability, making them potential candidates for future PDE5 inhibitors.
