AKR1C3 Inhibitory Potency of Naturally-occurring Amaryllidaceae Alkaloids of Different Structural Types

摘要

Aldo-keto reductase 1C3 (AKR1C3) is an important human enzyme that participates in the reduction of steroids and prostaglandins, which leads to proliferative signaling. AKR1C3 is frequently upregulated in various cancers, and this enzyme has been suggested as a therapeutic target for the treatment of these pathological conditions. The fact that the isoquinoline alkaloid stylopine has been identified as a potent AKR1C3 inhibitor has prompted us to screen a library of diverse types of Amaryllidaceae alkaloids, which biogenetically are isoquinoline alkaloids, on a recombinant form of AKRIC3. From the tested compounds, only tazettine showed moderate AKR1C3 inhibitory potency with an IC50 value of 15.8 +/- 1.2 mu M. Tazettine is a common Amaryllidaceae alkaloid, which could be used as a model substance for the further development of either analogues or related compounds with better inhibition potency.