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Bioorg Med Chem Lett. 2015 May 1;25(9):1827-30. doi: 10.1016/j.bmcl.2015.03.049. Epub 2015 Mar 24.

Fingerprint-based consensus virtual screening towards structurally new 5-HT(6)R ligands.

Author information

1
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.
2
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Kraków 31-343, Poland.
3
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.

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.

KEYWORDS:

Fingerprint-based consensus; Serotonin receptor 5-HT(6); Support vector machines; Virtual screening

PMID:
25866241
DOI:
10.1016/j.bmcl.2015.03.049
[Indexed for MEDLINE]

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