Amide-tethered quinoline-resorcinol conjugates as a new class of HSP90 inhibitors suppressing the growth of prostate cancer cells.
Amides
/ chemistry
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
HSP90 Heat-Shock Proteins
/ antagonists & inhibitors
Humans
Male
Models, Molecular
Molecular Structure
PC-3 Cells
Prostatic Neoplasms
/ drug therapy
Quinolines
/ chemistry
Resorcinols
/ chemistry
Structure-Activity Relationship
Tumor Cells, Cultured
Apoptosis
Cancer
Chaperone
Heat shock protein
Quinoline
Resorcinol
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
04
04
2019
revised:
09
07
2019
accepted:
11
07
2019
pubmed:
28
7
2019
medline:
22
10
2020
entrez:
27
7
2019
Statut:
ppublish
Résumé
The study is focused on the design and synthesis of amide tethered quinoline-resorcinol hybrid constructs as a new class of HSP90 inhibitor. In-vitro studies of the synthetic compounds led to the identification of compound 11, which possesses potent cell growth inhibitory effects against HCT116, Hep3B and PC-3 cell lines, exerted through HSP90 inhibition. Compound 11 triggers degradation of HSP90 client proteins along with concomitant induction of HSP70, demonstrates apoptosis inducing ability and causes G2M phase cell cycle arrest in PC-3 cells. Molecular modeling was used to dock compound 11 into the HSP90 active site and key interactions with the amino acid residues of the HSP90 chaperone protein were determined.
Identifiants
pubmed: 31349117
pii: S0045-2068(19)30530-9
doi: 10.1016/j.bioorg.2019.103119
pii:
doi:
Substances chimiques
Amides
0
Antineoplastic Agents
0
HSP90 Heat-Shock Proteins
0
Quinolines
0
Resorcinols
0
quinoline
E66400VT9R
resorcinol
YUL4LO94HK
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103119Informations de copyright
Copyright © 2019. Published by Elsevier Inc.