PUBLICATION
Novel Natural Product-like Caged Xanthones Bearing a Carbamate Moiety Exhibit Antitumor Potency and Anti-Angiogenesis Activity In vivo
- Authors
- Xu, X., Wu, Y., Hu, M., Li, X., Bao, Q., Bian, J., You, Q., Zhang, X.
- ID
- ZDB-PUB-180426-19
- Date
- 2016
- Source
- Scientific Reports 6: 35771 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents/chemistry
- Antineoplastic Agents/pharmacology*
- Antineoplastic Agents, Phytogenic/chemistry
- Antineoplastic Agents, Phytogenic/pharmacology
- Apoptosis/drug effects
- Biological Products/chemistry
- Biological Products/pharmacology*
- Cell Line, Tumor
- Drug Design
- Drug Screening Assays, Antitumor
- Female
- Garcinia/chemistry
- HCT116 Cells
- HSP90 Heat-Shock Proteins/antagonists & inhibitors
- Hep G2 Cells
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors
- Mice
- Mice, Nude
- Structure-Activity Relationship
- Xanthones/chemistry
- Xanthones/pharmacology*
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 27767192 Full text @ Sci. Rep.
Citation
Xu, X., Wu, Y., Hu, M., Li, X., Bao, Q., Bian, J., You, Q., Zhang, X. (2016) Novel Natural Product-like Caged Xanthones Bearing a Carbamate Moiety Exhibit Antitumor Potency and Anti-Angiogenesis Activity In vivo. Scientific Reports. 6:35771.
Abstract
DDO-6101, a simplified structure obtained from the Garcinia natural product (NP) gambogic acid (GA), has been previously shown to possess high cytotoxicity to a variety of human tumour cell lines. To improve its physicochemical properties and in vivo cytotoxic potency, a series of novel carbamate-bearing derivatives based on DDO-6101 was synthesized and characterized. The structural modifications revealed that the presence of a carbamate moiety was useful for obtaining comparable cytotoxicity and improved aqueous solubility and permeability. 8n, which contains a bipiperidine carbamate moiety, displayed better drug properties and potential in in vivo antitumor activity. In addition, an antitumor mechanistic study suggested that 8n (DDO-6337) inhibited the ATPase activity of Hsp90 (Heat shock protein 90), leading to the inhibition of HIF-1a and ultimately contributing to its anti-angiogenesis and antitumor properties.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping