Structure-activity relationship and mechanistic study on guggulsterone derivatives; Discovery of new anti-pancreatic cancer candidate.
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Discovery
Drug Screening Assays, Antitumor
Humans
Molecular Structure
Pancreatic Neoplasms
/ drug therapy
Pregnenediones
/ chemical synthesis
Proto-Oncogene Proteins c-akt
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Structure-Activity Relationship
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tumor Cells, Cultured
Anti-austerity agent
Drug discovery
Guggulsterone
Michael acceptor
Pancreatic cancer
Preferential cytotoxicity
Steroid
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 01 2022
15 01 2022
Historique:
received:
08
11
2021
revised:
06
12
2021
accepted:
07
12
2021
pubmed:
24
12
2021
medline:
24
2
2022
entrez:
23
12
2021
Statut:
ppublish
Résumé
Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as "Austerity". As a part of a research program aiming to develop a new-generation of anticancer agents, known as "anti-austerity agents", guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity. These agents are able to exert preferential cytotoxic activity only under nutrient-deprived conditions with little or no toxicity under normal conditions. In the present study, a library of 14 GSDs was synthesized and screened against PANC-1 human pancreatic cells. Among tested compounds, GSD-11 showed the most potent activity with PC
Identifiants
pubmed: 34942553
pii: S0968-0896(21)00571-X
doi: 10.1016/j.bmc.2021.116563
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Pregnenediones
0
pregna-4,17-diene-3,16-dione
A4PW148END
MTOR protein, human
EC 2.7.1.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116563Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.