Publication:
A Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening

dc.contributor.authorDebnath, Abhijit
dc.contributor.authorChaudhary, Hema
dc.contributor.authorSharma, Parul
dc.contributor.authorSingh, Rajesh
dc.contributor.authorSrivastava, Shikha
dc.date.accessioned2025-02-28T05:36:55Z
dc.date.available2025-02-28T05:36:55Z
dc.date.issued2024
dc.description.abstractBackground: 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 drug-likeness 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, mini-mal toxicity, and stability, making them potential candidates for future PDE5 inhibitors. © 2024 Bentham Science Publishers.
dc.identifier.doihttps://doi.org/10.2174/0115701808279586231221043744
dc.identifier.issn15701808
dc.identifier.urihttps://dl.bhu.ac.in/ir/handle/123456789/58279
dc.publisherBentham Science Publishers
dc.subjectADME profile
dc.subjectbenign prostatic hyperplasia
dc.subjecterectile dysfunction
dc.subjectPDE5
dc.subjectPDE5 inhibitors
dc.subjectpulmonary arterial hypertension
dc.titleA Deep Dive into PDE5 Inhibition: Innovative Discoveries via Virtual Screening
dc.typeArticle
dspace.entity.typePublication
journal.titleLetters in Drug Design and Discovery
journalvolume.identifier.volume21

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