Amide alkaloids from the fruits of Piper longum L. and their bioactivities.

Eight previously undescribed amide alkaloids [1-5], including three pairs of enantiomers [(±)-3, (±)-4, and (±)-5], along with 17 known compounds (6-22), were isolated from the fruits of Piper longum L with chromatographic techniques and chiral separation. The planar structures and relative configurations of these compounds were elucidated using HRESIMS and NMR analyses, while the absolute configurations were determined by electronic circular dichroism (ECD) calculations. Compounds 1-22 were assessed for their in vitro NO inhibition, cytotoxic, and anti-diabetic activities. Compounds (+)-5, 7, and 8 showed moderate NO inhibitory activity (10 μM < IC50 < 30 μM). Compounds 1, 9, and 13 exhibited significant cytotoxic effects against HeLa cells, with IC50 values of 9.99 ± 0.62, 6.25 ± 0.32, and 9.61 ± 0.48 μM, respectively. Compounds (+)-4, 7, 8, 9, 11, 12, 13, 15, and 16 showed potent cytotoxicity against HT-29 cells with IC50 values ranging from 2.65 to 7.78 μM. Compounds (+)-4, 6, and 16 exhibited weak cytotoxicity against MCF-7 cells (IC50 > 30 μM). Additionally, compound 6 showed moderate inhibitory activity against α-glucosidase with an IC50 of 112.03 ± 3.69 μM, whereas compound 8 significantly inhibited PTP1B, with an IC50 of 9.06 ± 0.68 μM. These findings offer valuable insights into the potential application of amide alkaloids from P. longum in developing functional foods and pharmaceuticals, highlighting their promise in health promotion.