Steroid sulfatase inhibiting lanostane triterpenes - Structure activity relationship and in silico insights.
Basidiomycota
/ chemistry
Coriolaceae
/ chemistry
Dose-Response Relationship, Drug
Enzyme Inhibitors
/ chemistry
Humans
Lanosterol
/ analogs & derivatives
Ligands
Models, Molecular
Molecular Structure
Reishi
/ chemistry
Steryl-Sulfatase
/ antagonists & inhibitors
Structure-Activity Relationship
Triterpenes
/ chemistry
Lanostane-type triterpenes
Molecular docking
Polypores
Steroid sulfatase
Virtual screening
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
02
10
2019
revised:
19
11
2019
accepted:
04
12
2019
pubmed:
20
12
2019
medline:
2
3
2021
entrez:
20
12
2019
Statut:
ppublish
Résumé
Steroid sulfatase (STS) transforms hormone precursors into active steroids. Thus, it represents a target of intense research regarding hormone-dependent cancers. In this study, three ligand-based pharmacophore models were developed to identify STS inhibitors from natural sources. In a pharmacophore-based virtual screening of a curated molecular TCM database, lanostane-type triterpenes (LTTs) were predicted as STS ligands. Three traditionally used polypores rich in LTTs, i.e., Ganoderma lucidum Karst., Gloeophyllum odoratum Imazeki, and Fomitopsis pinicola Karst., were selected as starting materials. Based on eighteen thereof isolated LTTs a structure activity relationship for this compound class was established with piptolinic acid D (1), pinicolic acid B (2), and ganoderol A (3) being the most pronounced and first natural product STS inhibitors with IC
Identifiants
pubmed: 31855822
pii: S0045-2068(19)31636-0
doi: 10.1016/j.bioorg.2019.103495
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Ligands
0
Triterpenes
0
Lanosterol
1J05Z83K3M
STS protein, human
EC 3.1.6.2
Steryl-Sulfatase
EC 3.1.6.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103495Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.