Two new compounds with cytotoxic activity on the human melanoma A375-S2 cells from Daphne giraldii callus cells.

Four compounds were isolated from Daphne giraldii callus cells, and their structures were characterized as daphnenone (1), daphnolon (2), R-(−)-1-(4′-hydroxyphenyl)-3-hydroxy-5-phenyl-1,5-pentandione (3), and S-(+)-daphneolone-4′-O-β-d-glucoside (4) on the basis of MS, NMR spectrographic analysis, and chemical methods. All of the four compounds possessed C6-C5-C6 carbon skeleton, and among them, 3 and 4 were two new compounds. In activity screening test, compounds 1, 2, 3, and 4 showed different degrees of cytotoxic activity against the tumor cells of human melanoma A375-S2 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium hydrobromide method, with IC50 values of 29.8, 51.0, 41.0, and 150.0 μM, respectively. Furthermore, we found the important target which could explain the cytotoxic mechanism of the four compounds by using autodock 4.0, a structure-guided discovery approach, and the important residues CYS532, GLY534, and SER535 of B-Raf kinase have been discovered. [ABSTRACT FROM AUTHOR]