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Table 3 Most relevant sirtuin activators

From: Sirtuin functions and modulation: from chemistry to the clinic

Compound Structure Enzyme activity Biological Effects Reference(s)
34,
resveratrol
SIRT1 EC1.5 a = 46.2 μM Improves mitochondrial functions and protects against fat diet-induced obesity (DIO). In obese mice leads to increased health-span and lifespan.
Promising effects and in clinical trials for the treatment of some diseases of aging (metabolic disorders, type 2 diabetes, etc.).
[9196, 106109]
35-37 35 SIRT1 EC1.5 = 2.9 μM
SIRT1 max act.b 447%
36 SIRT1 EC1.5 = 0.16 μM
SIRT1 max act. 781%
37 SIRT1 EC1.5 = 0.36 μM
SIRT1 max act. 296%
All SRT compounds, with different potencies, improve insulin sensitivity in DIO and genetically obese mice (Lepob/ob), lower plasma glucose and increase mitochondrial capacity.
In Zucker fa/fa rats, improve whole-body glucose homeostasis, insulin sensitivity in adipose tissue, skeletal muscle and liver, and mitochondrial bioenergetics in a SIRT-1 dependent manner.
Very good activities in different age-related disease conditions.
[95, 97101]
38,
STAC-8
SIRT1 EC1.5 = 1.2 μM
SIRT1 max act. 890%
Promising activities in different age-related disease models: obesity and metabolic disorders, inflammatory and autoimmune disorders, cardiovascular disease, hepatic steatosis, neurodegeneration, and cancer. [99101]
39 SIRT1 EC1.5 = 0.5 μM
SIRT1 max act. 220%
Not reported. [99102]
40, 41 40 SIRT1 EC1.5 = 0.3 μM
SIRT1 max act. 253%
41 SIRT1 EC1.5 = 0.4 μM
SIRT1 max act. 820%
Not reported. [99102]
42-44 EC1.5 < 250 nM
SIRT1 max act. ≥300%
Not reported. [99101, 103]
45,
STAC-5
SIRT1 EC1.5 = 0.4 μM
SIRT1 max act. 1310%
Promising activities in different age-related disease models: obesity and metabolic disorders, inflammatory and autoimmune disorders, cardiovascular disease, hepatic steatosis, neurodegeneration, and cancer. [99101, 104]
46 46a (MC2562) (Ar = Ph, R1 = OEt, R2 = benzyl):
SIRT1 EC1.5 ≈ 1 μM
SIRT2 EC1.5 = 25 μM
SIRT3 EC1.5 ≈ 50 μM
Induce α-tubulin hypoacetylation in U937 cells and reduce the number of senescent cells of 30-40% in human mesenchymal stem cells.
Increase NO release in HaCat cells, and accelerate tissue renewal in a mouse model of skin repair. In C2C12 myoblasts improve mitochondrial density and functions through activation of the SIRT1/AMPK axis. A water-soluble analog displays antiproliferative effect and increased H4K16 deacetylation in a panel of human cancer cells at 8-35 μM
[111113]
47,
honokiol
Increases SIRT3 levels by nearly two-fold @5μM and 10μM in cardiomyocytes after 24h treatment.
In vitro directly binds to SIRT3 and increases the affinity of SIRT3 for NAD+.
Blocks hypertrofic response of cardiomyocytes in vitro.
Protects mice from developing cardiac hypertrophy, attenuates pre-established cardiac hypertrophy in mice, reduces ROS production and prevents cardiomyocyte death in a SIRT3-dependent manner.
[114]
  1. aConcentration of compound required to increase enzyme activity by 50 %
  2. bMaximum percentage of activation achieved at the highest tested dose