Back to Search
Start Over
Synthesis of new glycosylated flavonoids with inhibitory activity on cell growth
- Source :
- Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP, Molecules; Volume 23; Issue 5; Pages: 1093, Molecules, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
- Publication Year :
- 2018
- Publisher :
- MDPI, 2018.
-
Abstract
- Natural flavonoids and xanthone glycosides display several biological activities, with the glycoside moiety playing an important role in the mechanism of action of these metabolites. Herein, to give further insights into the inhibitory activity on cell growth of these classes of compounds, the synthesis of four flavonoids (5, 6, 9, and 10) and one xanthone (7) containing one or more acetoglycoside moieties was carried out. Acetyl groups were introduced using acetic anhydride and microwave irradiation. The introduction of one or two acetoglycoside moieties in the framework of 3,7-dihydroxyflavone (4) was performed using two synthetic methods: the Michael reaction and the Koenigs-Knorr reaction. The in vitro cell growth inhibitory activity of compounds 5, 6, 7, 9, and 10 was investigated in six human tumor cell lines: A375-C5 (malignant melanoma IL-1 insensitive), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), U251 (glioblastoma astrocytoma), U373 (glioblastoma astrocytoma), and U87MG (glioblastoma astrocytoma). The new flavonoid 3-hydroxy-7-(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl) flavone (10) was the most potent compound in all tumor cell lines tested, with GI50 values < 8 µM and a notable degree of selectivity for cancer cells. © 2018 by the authors. Funding: This work was supported through national funds provided by Foundation for Science and Technology from the Minister of Science, Technology and Higher Education (FCT/MCTES-PIDDAC) and European Regional Development Fund (ERDF) through the COMPETE—Programa Operacional Factores de Competitividade (POFC) (POCI-01-0145-FEDER-016790), PPCDT—Promover a Produção Científica e Desenvolvimento Tecnológico e a Constituição de Redes Temáticas (Project 3599), under the project PTDC/MAR-BIO/4694/2014 in the framework of the programme PT2020 and INNOVMAR—Innovation and Sustainability in the Management and Exploitation of Marine Resources, reference NORTE-01-0145-FEDER-000035, Research Line NOVELMAR in the framework of North Portugal Regional Operational Programme (NORTE 2020). Acknowledgments: Marta Correia-da-Silva thanks FCT for the postdoctoral fellowship SFRH/BPD/81878/2011 and Ana R. Neves and Patrícia M.A. Silva for the Ph.D. fellowships SFRH/BD/114856/2016 and SFRH/BD/90744/2012, respectively.
- Subjects :
- Glycosylation
growth inhibitory activity
synthesis
glia
Flavonoid
Pharmaceutical Science
IC50
MCF-7 cell line
01 natural sciences
Analytical Chemistry
chemistry.chemical_compound
Drug Discovery
Xanthone
flavonoids
xanthones
acetylation
glycosylation
Microwaves
antineoplastic agent
chemistry.chemical_classification
Chemistry
drug effect
Acetylation
Biochemistry
Chemistry (miscellaneous)
xanthone
MCF-7 Cells
Molecular Medicine
Neuroglia
drug design
Cell Survival
Xanthones
Acetic Anhydrides
Antineoplastic Agents
acetic anhydride
010402 general chemistry
chemistry
Article
Inhibitory Concentration 50
Structure-Activity Relationship
astrocyte
Cell Line, Tumor
Structure–activity relationship
Humans
flavonoid
human
Physical and Theoretical Chemistry
xanthone derivative
structure activity relation
Flavonoids
010405 organic chemistry
Cell growth
Organic Chemistry
tumor cell line
Glycoside
Epithelial Cells
0104 chemical sciences
microwave radiation
Cell culture
Drug Design
Astrocytes
Cancer cell
pathology
epithelium cell
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP, Molecules; Volume 23; Issue 5; Pages: 1093, Molecules, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
- Accession number :
- edsair.doi.dedup.....2d7b722cfd5445223b0b25308de8fa3c