Pharmacophore and molecular docking based identification of novel structurally diverse PDE-5 inhibitors

Autor:	Anubhuti Pandey, Aarti Singh, Sarvesh Paliwal, Anupama Mittal, Mukta Sharma, Shailendra Paliwal
Rok vydání:	2014
Předmět:	Virtual screening biology Chemistry Stereochemistry Organic Chemistry Pharmacology toxicology Druggability Active site biology.protein Identification (biology) General Pharmacology Toxicology and Pharmaceutics Pharmacophore Amino acid residue Discovery Studio
Zdroj:	Medicinal Chemistry Research. 24:576-587
ISSN:	1554-8120 1054-2523
Popis:	In view that PDE5 is a potential target for the design of antihypertensive drugs a pharmacophore and molecular docking based virtual screening protocol was implemented. Two hydrophobic and one ring aromatic feature containing pharmacophore model was developed, validated, and used to mine Maybridge chemical compound database. This led to retrieval of many hits which were screened on the basis of estimated activity, fit value, and Lipinski’s violation. The eight selected hits were docked into the active site of PDE5 to evaluate the specific inhibitor-enzyme interactions finally leading to identification of two potent, druggable PDE5 inhibitors with good LibDock scores. Both the compounds showed interaction with Gln 817, Tyr 612, and Ala 767 amino acid residues testifying the results obtained from pharmacophore modeling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::010e1b6b5371d1fec5980615a9b5fab4 https://doi.org/10.1007/s00044-014-1144-4 Zobrazit plný text záznamu Full text from SpringerLink