title: Fingerprint-based consensus virtual screening towards structurally new 5-HT(6)R ligands.
abstract: Virtual screening towards the search of new 5-HT6R ligands was carried out with three different fingerprints used for molecules representation. Two structurally new compounds were found to be characterized by a significant 5-HT6R activity (Ki of 119 and 670 nM). The compounds do not possess a positive ionizable group in their structures and therefore they belong to the group of atypical, non-basic 5-HT6R ligands. The obtained hits were proved to fit well in the 5-HT6R binding cavity by docking and molecular dynamic simulation experiments. Moreover, an in silico evaluation of the ADMET properties of these compounds predicted their drug-like character.
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków 31-343, Poland; Faculty of Chemistry, Jagiellonian University, 3 Ingardena Street, Kraków 30-060, Poland.
authors: Sabina
authors: S
authors: Smusz
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków 31-343, Poland.
authors: Rafał
authors: R
authors: Kurczab
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków 31-343, Poland.
authors: Grzegorz
authors: G
authors: Satała
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków 31-343, Poland. Electronic address: bojarski@if-pan.krakow.pl.
authors: Andrzej J
authors: AJ
authors: Bojarski
mesh_terms: D000818:Animals; D016466:CHO Cells; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000378:metabolism*
chemical_list: D008024:Ligands; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor
keywords: Fingerprint-based consensus; Serotonin receptor 5-HT(6); Support vector machines; Virtual screening