Disubstituted naphthyl β-D-xylopyranosides : Synthesis, GAG priming, and histone acetyltransferase (HAT) inhibition
Författare
Summary, in English
Xylosides are a group of compounds that can induce glycosaminoglycan (GAG) chain synthesis independently of a proteoglycan core protein. We have previously shown that the xyloside 2-(6-hydroxynaphthyl)β-D-xylopyranoside has a tumor-selective growth inhibitory effect both in vitro and in vivo, and that the effect in vitro was correlated to a reduction in histone H3 acetylation. In addition, GAG chains have previously been reported to inhibit histone acetyltransferases (HAT). To investigate if xylosides, or the corresponding xyloside-primed GAG chains, can be used as HAT inhibitors, we have synthesized a series of naphthoxylosides carrying structural motifs similar to the aromatic moieties of the known HAT inhibitors garcinol and curcumin, and studied their biological activities. Here, we show that the disubstituted naphthoxylosides induced GAG chain synthesis, and that the ones with at least one free phenolic group exhibited moderate HAT inhibition in vitro, without affecting histone H3 acetylation in cell culture. The xyloside-primed GAG chains, on the other hand, had no effect on HAT activity, possibly explaining why the effect of the xylosides on histone H3 acetylation was absent in cell culture as the xylosides were recruited for GAG chain synthesis. Further investigations are required to find xylosides that are effective HAT inhibitors or xylosides producing GAG chains with HAT inhibitory effects.
Avdelning/ar
- Centrum för analys och syntes
- Institutionen för experimentell medicinsk vetenskap
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2016-04
Språk
Engelska
Sidor
57-245
Publikation/Tidskrift/Serie
Glycoconjugate Journal
Volym
33
Issue
2
Dokumenttyp
Artikel i tidskrift
Förlag
Springer
Ämne
- Biochemistry and Molecular Biology
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1573-4986