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]