Pharmacophore based virtual screening, molecular docking and biological evaluation to identify novel PDE5 inhibitors with vasodilatory activity.

Abstract

Prompted by the role of PDE5 and its closely associated cAMP and cGMP in hypertension, we have attempted to discover novel PDE5 inhibitors through ligand based virtual screening. Rigorously validated model comprising of one HBA, one HY and one RA was used as a query to search the NCI database leading to retrieval of many compounds which were screened on the basis of estimated activity, fit value and Lipinski's violation. Selected compounds were subjected to docking studies which resulted into visualization of potential interaction capabilities of NCI compounds in line to pharmacophoric features. Finally three compounds were subjected to in vitro evaluation using the isolated rat aortic model. The results showed that all three compounds are potent and novel PDE5 inhibitors with vasodilatory activity range from 10(-2) to 10(-5) M.

• Authors: Anupama Mittal, Sarvesh Paliwal, Mukta Sharma, Aarti Singh, Swapnil Sharma, Divya Yadav
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 24 Issue 14 Pg. 3137-41 (Jul 15 2014) ISSN: 1464-3405 [Electronic] England
• PMID: 24856068 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Phosphodiesterase 5 Inhibitors
• Vasodilator Agents
• Cyclic Nucleotide Phosphodiesterases, Type 5

Topics

• Cyclic Nucleotide Phosphodiesterases, Type 5 (metabolism)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Humans
• Molecular Docking Simulation
• Molecular Structure
• Phosphodiesterase 5 Inhibitors (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Vasodilation (drug effects)
• Vasodilator Agents (chemical synthesis, chemistry, pharmacology)