SZC-6, a small-molecule activator of SIRT3, attenuates cardiac hypertrophy in mice.

ABSTRACT: Sirtuin3 (SIRT3), a class III histone deacetylase, is implicated in various cardiovascular diseases as a novel therapeutic target. SIRT3 has been proven to be cardioprotective in a model of Ang II-induced cardiac hypertrophy. However, a few small-molecule compounds targeting deacetylases could activate SIRT3. In this study, we generated a novel SIRT3 activator, 3-(2-bromo-4-hydroxyphenyl)-7-hydroxy-2H-chromen-2-one (SZC-6), through structural optimization of the first SIRT3 agonist C12. We demonstrated that SZC-6 directly bound to SIRT3 with K_d value of 15 μM, and increased SIRT3 deacetylation activity with EC₅₀ value of 23.2 ± 3.3 µM. In neonatal rat cardiomyocytes (NRCMs), pretreatment with SZC-6 (10, 20, 40 µM) dose-dependently attenuated isoproterenol (ISO)-induce

SUBMITTER: Li ZY 

PROVIDER: S-EPMC9958013 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature