Pyripyropene A

Pyripyropene A is an orally active, potent, and highly selective SOAT2/ACAT2 inhibitor with a half-maximal inhibitory concentration (IC50) as low as 0.07 µM. Pyripyropene A alleviates hypercholesterolemia and inhibits the progression of atherosclerosis.

HUVECs:1.8 μM, ACAT2:0.07 µM

Method: Human umbilical vein endothelial cells (HUVECs) were treated with Pyripyropene A (0.05–20 μM) for 72 h, and cell proliferation inhibition was measured using the WST-8 colorimetric assay.
Result: Pyripyropene A inhibited HUVEC proliferation with an IC50 of 1.8 μM and exhibited a cytostatic effect (rather than cytotoxicity) within the range of 0.05–20 μM. No inhibitory effect was observed on KB3-1, K562, or Neuro2A cells even at a concentration of 100 μM [1].
Method: HUVECs were pretreated with Pyripyropene A (0.0001–10 μM) for 12 h, stimulated with VEGF (20 ng/mL) for 24 h, and cell migration was assessed using the chemotaxis chamber method.
Result: Pyripyropene A dose-dependently inhibited VEGF-induced HUVEC migration. At a concentration of 10 μM, the number of migrated cells was reduced to less than 5% of the control group [1].
Method: Chinese hamster ovary (CHO) cells expressing African green monkey SOAT1 or SOAT2 (SOAT1-CHO and SOAT2-CHO cells) were treated with Pyripyropene A and its synthetic analogs for 6 hours. Following labeling with [1-¹⁴C]oleic acid, the synthesis of [¹⁴C]cholesteryl ester (CE) was separated and quantified by TLC to calculate SOAT inhibitory activity.
Result: Pyripyropene A exhibited potent and selective inhibitory activity against SOAT2, with an IC50 of 0.07 μM, while the IC50 for SOAT1 was >80 μM, resulting in a selectivity index (SI) of >1000. A-ring simplified analogs 7 and 10 demonstrated SOAT2 inhibitory activity comparable to that of natural Pyripyropene A, along with exceptionally high isozyme selectivity as synthetic compounds [2].

Method: C57BL/6 mice (n=5/group) were orally administered Pyripyropene A (1, 10, 50, 100 mg/kg), and 30 minutes later, [¹⁴C]cholesterol was orally gavaged. Feces were collected for 48 hours, and the intestinal cholesterol absorption rate was measured using the fecal dual-isotope method.
Result: Pyripyropene A dose-dependently inhibited intestinal cholesterol absorption, with inhibition rates of 30.5±4.7%, 48.9±2.2%, and 55.8±3.3% at doses of 10, 50, and 100 mg/kg, respectively [3].

Methanol: 8 mg/mL (13.71 mM), Sonication is recommended.