Novel xanthone derivatives as potent sirtuin 2 inhibitors

[Display omitted] Six amino derivatives of xanthone were obtained via chemical synthesis. Biochemical studies revealed their SIRT2 inhibitory activity ranging from 48.5 % (compound 4, 5-chloro-2-((4-(3-methoxyphenyl)piperazin-1-yl)methyl)-9H-xanthen-9-one hydrochloride) to 93.2 % (compound 3, 5-chlo...

Full description

Saved in:

Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 100; p. 129620
Main Authors:	Mazur, Gabriela, Pańczyk-Straszak, Katarzyna, Krysińska, Karolina, Niemiec, Karolina, Waszkielewicz, Anna
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-03-2024
Subjects:	Amines Lipophilicity SIRT2 Sirtuins Xanthone Sirtuins Xanthone Amines SIRT2 Lipophilicity
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	[Display omitted] Six amino derivatives of xanthone were obtained via chemical synthesis. Biochemical studies revealed their SIRT2 inhibitory activity ranging from 48.5 % (compound 4, 5-chloro-2-((4-(3-methoxyphenyl)piperazin-1-yl)methyl)-9H-xanthen-9-one hydrochloride) to 93.2 % (compound 3, 5-chloro-2-(((2-methoxyphenethyl)amino)methyl)-9H-xanthen-9-one hydrochloride). The structure–activity analysis showed favourable properties of secondary amines relative to tertiary piperazine derivatives. The tested compounds do not possess additional SIRT1 activating activity and no antioxidant activity (DPPH in vitro assay). Comprehensive analysis of the lipophilicity of the obtained compounds was also performed. For compound 3 potential molecular targets and similar active compounds were predicted in order to facilitate further research in this group of compounds.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2024.129620