Novel xanthone derivatives as potent sirtuin 2 inhibitors

Bioorg Med Chem Lett. 2024 Jan 26;100:129620. doi: 10.1016/j.bmcl.2024.129620. Online ahead of print.ABSTRACTSix 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.PMID:38280655 | DOI:10.1016/j.bmcl.2024.129620
Source: Bioorganic and Medicinal Chemistry Letters - Category: Chemistry Authors: Source Type: research