1. Two new compounds with cytotoxic activity on the human melanoma A375-S2 cells from Daphne giraldii callus cells.
- Author
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Wang LB, Dong NW, Wu ZH, and Wu LJ
- Subjects
- Antineoplastic Agents, Phytogenic chemistry, Benzene Derivatives chemistry, Drug Screening Assays, Antitumor, Drugs, Chinese Herbal chemistry, Glucosides chemistry, Humans, Melanoma pathology, Molecular Structure, Antineoplastic Agents, Phytogenic isolation & purification, Antineoplastic Agents, Phytogenic pharmacology, Benzene Derivatives isolation & purification, Benzene Derivatives pharmacology, Daphne chemistry, Drugs, Chinese Herbal isolation & purification, Drugs, Chinese Herbal pharmacology, Glucosides isolation & purification, Glucosides pharmacology
- Abstract
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 IC(50) 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.
- Published
- 2012
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