Table 3 Most relevant sirtuin activators

34,

resveratrol

SIRT1 EC_1.5 ^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.).

[91–96, 106–109]

35-37

35 SIRT1 EC_1.5 = 2.9 μM

SIRT1 max act.^b 447%

36 SIRT1 EC_1.5 = 0.16 μM

SIRT1 max act. 781%

37 SIRT1 EC_1.5 = 0.36 μM

SIRT1 max act. 296%

All SRT compounds, with different potencies, improve insulin sensitivity in DIO and genetically obese mice (Lep^ob/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, 97–101]

38,

STAC-8

SIRT1 EC_1.5 = 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.

[99–101]

39

SIRT1 EC_1.5 = 0.5 μM

SIRT1 max act. 220%

Not reported.

[99–102]

40, 41

40 SIRT1 EC_1.5 = 0.3 μM

SIRT1 max act. 253%

41 SIRT1 EC_1.5 = 0.4 μM

SIRT1 max act. 820%

Not reported.

[99–102]

42-44

EC_1.5 < 250 nM

SIRT1 max act. ≥300%

Not reported.

[99–101, 103]

45,

STAC-5

SIRT1 EC_1.5 = 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.

[99–101, 104]

46

46a (MC2562) (Ar = Ph, R₁ = OEt, R₂ = benzyl):

SIRT1 EC_1.5 ≈ 1 μM

SIRT2 EC_1.5 = 25 μM

SIRT3 EC_1.5 ≈ 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

[111–113]

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]