Nitidine from Zanthoxylum rhetsa and its cytotoxic activities in vitro and in silico ADMET properties

Nitidine, a potential medicinal natural benzophenanthridine alkaloid, has expressed various bioactivities such as antibacterial, antifungal, antiviral, anti-inflammatory, analgesic, and notably cytotoxicity. In this study, nitidine was isolated from trunk of Zanthoxylum rhetsa (Rutaceae) and its structure was elucidated by spectral data (1D and 2D NMR; and MS). The cytotoxicity of nitidine was assessed in vitro against five cancer cell lines, and normal cell line Vero. As the results, nitidine exhibited potent inhibitory activity against KB, LU-1, HepG2, LNCaP and MCF7 cell lines with IC50 values of 0.28, 0.26, 0.27, 0.25 and 0.28 mu m, respectively, while low-cytotoxicity against normal cell line Vero with IC50 value of 140.65 mu m. Comparing cytotoxic activity of nitidine with docking analysis in previous study, nitidine formed hydrogen bonds with residues Asn101 and Ala317 of tubulin and had a docking score of -14.45 kcal/mol, all the data proved nitidine would be a potential candidate for inhibiting the function of tubulin at the active site regarding binding affinity, dock pose, and ADMET-where ADMET stands for absorption, distribution, metabolism, excretion and toxicity-properties analysis.