Aim of the study
Human 3β-Hydroxysteroid dehydrogenase 2 (h3β-HSD2) catalyzes the formation of precursors for sex hormones and corticosteroids, which play critical roles in reproduction and metabolism. We explored inhibition and mode action of chalcones of inhibiting h3β-HSD2 and compared it with rat 3β-HSD1. Materials and
Conclusion
Some chalcones are potent h3β-HSD2 and r3β-HSD1 inhibitors, possibly being potential drugs to treat Cushing's syndrome or polycystic ovarian syndrome.
Methods
We investigated the inhibition of 5 chalcones on h3β-HSD2 and compared species-dependent difference with 3β-HSD1.
Results
The inhibitory strength on h3β-HSD2 was isoliquiritigenin (IC50, 0.391 μM) > licochalcone A (0.494 μM) > licochalcone B (1.485 μM) > echinatin (1.746 μM) >chalcone (100.3 μM). The inhibitory strength on r3β-HSD1 was isoliquiritigenin (IC50, 0.829 μM) > licochalcone A (1.165 μM) > licochalcone B (1.866 μM) > echinatin (2.593 μM) > chalcone (101.2 μM). Docking showed that all chemicals bind steroid and/or NAD+-binding site with the mixed mode. Structure-activity relationship analysis showed that strength was correlated with chemical's hydrogen bond acceptor.