- 生物活性
α-NETA 是一种有效的，非竞争性的胆碱乙酰转移酶 (ChA) 抑制剂，IC50 为 9 μM。α-NETA 是一种有效的 ALDH1A1 (IC50=0.04 µM) 和趋化因子样受体 1 (CMKLR1) 拮抗剂。α-NETA 微弱的抑制胆碱酯酶 (ChE; IC50=84 µM) 和乙酰胆碱酯 (AChE; IC50=300 µM)。α-NETA 具有抗癌活性。
- 靶点
IC50: 9 μM (ChAT); 0.04 µM (ALDH1A1); CMKLR1; 84 µM (ChE); 300 µM (AChE)
- 体外研究
α-NETA (50-150 nM; 24 hours) decreases all cell lines viability in a dose-dependent manner.
α-NETA (2.5-10.0 µg/mL; 24 hours) leads to epithelial ovarian cancer (EOC) cell death associated with membrane blistering and cytoplasm leakage.
α-NETA treatment increases EOC cell expression of pyroptosis-associated proteins.
α-NETA is most potent in inhibiting aldehyde dehydrogenase 1 family, member A1 (ALDH1A1; IC
50
=0.04 µM; purified enzymes assay), followed by CMKLR1 (IC
50
=0.375 µM for β-ARR2 recruitment; Cell-based assay) and G9a histone lysine methyltransferase (IC
50
=0.50 µM; purified enzymes assay). α-NETA selectively inhibits chemerin-stimulated CMKLR1 association with β-arrestin2.
α-NETA possesses fluorescent characteristics (excitation spectrum: maxima 255 and 297 nm; emission spectrum: maximum 437 nm) of naphthyl moiety.
Cell Viability Assay
Cell Line:
Ho8910, Ho8910PM, A2780, and Iose80 cells
Concentration:
50, 100, 150 nM
Incubation Time:
24 hours
Result:
Decreased all cell lines viability in a dose-dependent manner.
Apoptosis Analysis
Cell Line:
Epithelial ovarian cancer (EOC) cell
Concentration:
2.5, 7.5, 10.0 µg/mL
Incubation Time:
24 hours
Result:
Led to EOC cell death associated with membrane blistering and cytoplasm leakage.
- 体内研究
α-NETA (i.p.; 0.125 mg/kg; once every other day for 20 days) significantly decreases tumor volume and tumor weight.
α-NETA (s.c. injection; 3 mg/kg or 10 mg/kg; daily; for 30 days) significantly delays the onset of EAE with 3 mg/kg, and completely suppresses clinical signs for an average of nine days with 10 mg/kg beyond the first appearance of disease in control female C57BL/6 mice.
Animal Model:
BALB/c nude mice with skov3 cells
Dosage:
0.125 mg/kg
Administration:
IP; once every other day for 20 days
Result:
Significantly decreased tumor volume and tumor weight.
