NMR-guided discovery of bioactive hydroxyl-amide alkaloids from Piper longum L. fruits

Piper longum L. (Piperaceae), a distinctive spice, is extensively utilized in traditional cuisines across different countries. Despite the rich content in P. longum fruits, studies on isolation and biological activity of hydroxyamide alkaloids are limited. An NMR-guided analytical strategy was applied to rapidly isolate and identify 42 hydroxyamide alkaloids, including 34 previously unreported compounds. The absolute configurations of the uncharacterized compounds were determined based on spectrascopic data, ECD and quantum calculations, together with chemical derivatization. Additionally, bioactivities of these compounds were assessed. Six compounds exhibited weak anti-inflammatory activity, and five compounds presented anti-proliferative effects on cancer cell lines including HeLa (human cervical carcinoma cells), HT-29 (human colorectal adenocarcinoma cells), and MCF-7 (human breast adenocarcinoma cells), with the most pronounced effects observed against HT-29 cells. These unique phytochemicals show promise for the development of functional products derived from P. longum fruits.