2. Academic Validation
  3. Novel xanthone derivatives as potent sirtuin 2 inhibitors

Novel xanthone derivatives as potent sirtuin 2 inhibitors

  • Bioorg Med Chem Lett. 2024 Mar 1:100:129620. doi: 10.1016/j.bmcl.2024.129620.
Gabriela Mazur 1,  Katarzyna Pańczyk-Straszak 1,  Karolina Krysińska 1,  Karolina Niemiec 1,  Anna Waszkielewicz 2
Affiliations

Affiliations

  • 1 Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
  • 2 Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: [email protected].
PMID: 38280655 DOI: 10.1016/j.bmcl.2024.129620
Abstract

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.

Keywords

Amines; Lipophilicity; SIRT2; Sirtuins; Xanthone.

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