title: 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.affiliation: Department of Pharmacy, Banasthali University, P.O. Banasthali, Rajasthan 304022, India. Electronic address: anupamamitt@gmail.com.
authors.forename: Anupama
authors.initials: A
authors.lastname: Mittal
authors.affiliation: Department of Pharmacy, Banasthali University, P.O. Banasthali, Rajasthan 304022, India. Electronic address: paliwalsarvesh@yahoo.com.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Paliwal
authors.affiliation: Department of Pharmacy, Banasthali University, P.O. Banasthali, Rajasthan 304022, India. Electronic address: sharmamukta.924@gmail.com.
authors.forename: Mukta
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Pharmacy, Banasthali University, P.O. Banasthali, Rajasthan 304022, India. Electronic address: aartifab@gmail.com.
authors.forename: Aarti
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Pharmacy, Banasthali University, P.O. Banasthali, Rajasthan 304022, India. Electronic address: swapnilsharma1978@gmail.com.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Pharmacy, Banasthali University, P.O. Banasthali, Rajasthan 304022, India. Electronic address: divyavirgo2002@gmail.com.
authors.forename: Divya
authors.initials: D
authors.lastname: Yadav
mesh_terms: D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D058986:Phosphodiesterase 5 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D014665:Vasodilator Agents; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5
keywords: Cyclic adenosine monophosphate; Cyclic guanosine monophosphate; Discovery studio; Hydrogen bond acceptor; Phosphodiesterase-5