Pharmacophore modeling, virtual screening and molecular docking studies for identification of new inverse agonists of human histamine H1 receptor

Sundarapandian Thangapandian, Navaneethakrishnan Krishnamoorthy, Shalini John, Sugunadevi Sakkiah, Prettina Lazar, Yuno Lee, Keun Woo Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy.Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverseagonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.

Original languageEnglish
Pages (from-to)52-58
Number of pages7
JournalBulletin of the Korean Chemical Society
Volume31
Issue number1
DOIs
Publication statusPublished - 1 Jan 2010
Externally publishedYes

Fingerprint

Histamine H1 Receptors
Screening
Anti-Allergic Agents
Molecules
Rhodopsin
G-Protein-Coupled Receptors
Hydrogen bonds
Ligands
Amino Acids
Pharmaceutical Preparations

Keywords

  • Histamine H1 receptor
  • Inverse agonists
  • Ligandfit
  • Lipinski's rule
  • Pharmacophore

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Pharmacophore modeling, virtual screening and molecular docking studies for identification of new inverse agonists of human histamine H1 receptor. / Thangapandian, Sundarapandian; Krishnamoorthy, Navaneethakrishnan; John, Shalini; Sakkiah, Sugunadevi; Lazar, Prettina; Lee, Yuno; Lee, Keun Woo.

In: Bulletin of the Korean Chemical Society, Vol. 31, No. 1, 01.01.2010, p. 52-58.

Research output: Contribution to journalArticle

Thangapandian, Sundarapandian ; Krishnamoorthy, Navaneethakrishnan ; John, Shalini ; Sakkiah, Sugunadevi ; Lazar, Prettina ; Lee, Yuno ; Lee, Keun Woo. / Pharmacophore modeling, virtual screening and molecular docking studies for identification of new inverse agonists of human histamine H1 receptor. In: Bulletin of the Korean Chemical Society. 2010 ; Vol. 31, No. 1. pp. 52-58.
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