Antiproliferative piperidine alkaloids from the leaves of Alocasia macrorrhiza

Seventeen piperidine alkaloids, including 15 previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol alkaloids and a previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3-ol alkaloid, were isolated from the leaves of Alocasia macrorrhiza (L.) Schott. Their planar structures and configurations were elucidated based on HR-ESI-MS, 1D and 2D NMR, Snatzke's method, modified Mosher method, single-crystal X-ray crystallography, as well as quantum chemical calculation. It was found that ΔδH5b-H5a can be used to elucidate the relative configuration of 2,3,4,6-tetrasubstituted piperidine, by analyzing the NMR data of 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol. Antiproliferative activity was evaluated for all of the alkaloids, and compounds 6–8 showed considerable inhibitory activity against K562 cell line, with the IC50 values of 17.24 ± 1.62, 19.31 ± 0.9 and 18.77 ± 1.09μM, respectively. Furthermore, compounds 6 and 7 exerted an antiproliferative effect by inducing apoptosis. •Bioactive phytochemicals of the leaves of Alocasia macrorrhiza were studied.•Sixteen new piperidine alkaloids were isolated and identified.•Piperidine alkaloids have exhibited potential antiproliferative activity.•The relative configuration of piperidine can be elucidated by calculating ΔδH5b-H5a.•Alocasia macrorrhiza may be beneficial to cancer related diseases.