Antidiabetic and Cytotoxic Activities of Rotenoids and Isoflavonoids Isolated from Millettia pachycarpa Benth

[Image: see text] A phytochemical investigation of the root and leaf extracts of Millettia pachycarpa Benth resulted in the isolation and identification of 16 compounds, including six rotenoids (1–6) and 10 prenylated isoflavonoids (7–16). Compound 4 was isolated as a scalemic mixture, which was resolved by chiral HPLC to afford (−)-(6aS,12aS)-12a-hydroxy-α-toxicarol (4) and (+)–(6aR,12aR)-12a-hydroxy-α-toxicarol (4). (+)-(6aR,12aR)-Millettiapachycarpin (3) and (−)-(6aS,12aS)-12a-hydroxy-α-toxicarol (4) were isolated as new compounds. The absolute configuration of (−)-(6R)-pachycarotenoid (2), (+)–(6aR,12aR)-millettiapachycarpin (3), (−)-(6aS,12aS)-4 and (+)–(6aR,12aR)-12a-hydroxy-α-toxicarol (4), (+)-(6aS,12aS)-(5), and (−)-(6aS,12aS,2″R)-sumatrol (6) were identified by electronic circular dichroism (ECD) data. (−)-(6aS,12aS,2″R)-Sumatrol (6) was also confirmed by X-ray diffraction analysis using Cu–Kα radiation. Antidiabetic activities, including α-glucosidase and α-amylase inhibitory activities, and cytotoxicities against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells of some isolated compounds were evaluated. Of these, isolupalbigenin (11) exhibited the highest α-glucosidase inhibitory activity, with an IC(50) value of 11.3 ± 0.2 μM, whereas the scalemic mixture of 12a-hydroxy-α-toxicarol (4) displayed the best α-amylase inhibitory activity, with an IC(50) value of 106.9 ± 0.2 μM. Euchrenone b10 (15) exhibited the highest cytotoxicity against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells, with IC(50) values of 40.3, 39.1, and 15.1 μM, respectively. In addition, molecular docking simulations of α-glucosidase inhibition of the active compounds were studied.