Histamine H3 receptor ligands by hybrid virtual screening, docking, molecular dynamics simulations, and investigation of their biological effects

• DOI: 10.1111/cbdd.13471
• Publication Date: 2018-12-26T15:59:45Z
• Authors: Nakisa Ghamari; Omid Zarei; David Reiner; Siavoush Dastmalchi; Holger Stark; Maryam Hamzeh‐Miv...
• Keywords: Docking (animal)

Abstract Histamine H 3 receptors (H R), belonging to G‐protein coupled (GPCR) class A superfamily, are responsible for modulating the release of histamine as well other neurotransmitters by a negative feedback mechanism mainly in central nervous system (CNS). These have gained increased attention therapeutic target several CNS related neurological diseases. In current study, we aimed identify novel R ligands using silico virtual screening methods. To this end, combination ligand‐ and structure‐based approaches was utilized ZINC database on homology model human R. Structural similarity‐ pharmacophore‐based were employed generate compound libraries. Various molecular modeling methodologies such docking dynamics simulation along with different drug likeness filtering criteria applied select anti‐H promising candidate molecules based known parent lead compounds. vitro binding assays selected demonstrated three them being active within micromolar submicromolar K i range. The integrated computational experimental methods used work can provide new general insights systematic hit identification agents from large