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Intriguing steroid glycosides for cancer therapy by suppressing the DNA damage response and mTOR/S6K signaling pathways.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2024 Oct; Vol. 151, pp. 107619. Date of Electronic Publication: 2024 Jul 09. - Publication Year :
- 2024
-
Abstract
- Two rare 8-hydroxysteroid glycosides (6-7), and their downstream metabolites (1-5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8-14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1-14 on liver and lung cancer cell lines were evaluated, and preliminary structure-activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Structure-Activity Relationship
Molecular Structure
Cell Proliferation drug effects
Steroids chemistry
Steroids pharmacology
Steroids isolation & purification
Ribosomal Protein S6 Kinases metabolism
Ribosomal Protein S6 Kinases antagonists & inhibitors
Antineoplastic Agents, Phytogenic pharmacology
Antineoplastic Agents, Phytogenic chemistry
Antineoplastic Agents, Phytogenic isolation & purification
Cell Line, Tumor
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
TOR Serine-Threonine Kinases metabolism
TOR Serine-Threonine Kinases antagonists & inhibitors
Glycosides chemistry
Glycosides pharmacology
Glycosides isolation & purification
DNA Damage drug effects
Signal Transduction drug effects
Drug Screening Assays, Antitumor
Dose-Response Relationship, Drug
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 151
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 39024806
- Full Text :
- https://doi.org/10.1016/j.bioorg.2024.107619