生物活性

• 描述Sirtuin (Sirt) 1 and 2 are members of the NAD+-dependent class III histone deacetylase family that are involved in various cellular events, such as transcriptional silencing, chromatin remodeling, and lifespan duration. Salermide is a potent inhibitor of both Sirt1 and Sirt2. It dose-dependently inhibited human Sirt1 protein with 80% inhibition at 90μM. Salermide shows more efficient inhibitory effect on Sirt2 with 80% inhibition at 25μM. Treatment with 100μM Salermide for 24h induced the decrease of cell numbers in cancer cell lines derived from leukaemia (MOLT4, KG1A, K562), lymphoma (Raji), colon (SW480) and breast (MDA-MB-231) primary malignancies, but not in non-tumorigenic MRC5 cells. The IC₅₀ values of Salermide in MOLT4, MDA-MB-231 and SW480 cancer cells were around 20, 110, and 100 μM, respectively. After 72-h incubation with 100 μM Salermide, only 10% of KG1A cells and 50% of Raji and K562 cells were viable. An increase of cytosolic-activated caspase 3 and a decrease of mitochondrial-cytochrome c were observed in Salermide-treated cells 2h post treatment. Twenty-four-hour incubation of 25 and 100μM Salermide induced slight tubulin acetylation in MOLT4, MDA-MB-231 and SW480 cells. Intraperitoneal injection of 100μM Salermide over 34 days in nude mice showed no apparent toxicity as monitored by diet consumption, body-weight gain, and postural and behavioral changes.

• 动物研究
  剂量	Mice: 30 mg/kg[2] (i.p.)
  给药途径	i.p.