ABSTRACT
Plants in the family Aristolochiaceae contain phenanthrene skeleton-containing chemical constituents that exhibit nephrotoxic, carcinogenic, mutagenic, anti-inflammatory, and cytotoxic effects. Two new phenanthrene-containing 1,2-oxazin-6-ones, designated as asaroidoxazine A (1) and asaroidoxazine B (2), and a known aristolactam, 5-methoxyaristololactam I (3), were isolated from the roots of Asarum asaroides. The structures of compounds 1 and 2 were determined using spectroscopic methods and X-ray crystallography. Treatment of SH-SY5Y human neuroblastoma cells with 1 µM of asaroidoxazine A (1) induced nuclear condensation as well as caspase-3/7 activation, indicating that this compound is a strong apoptosis inducer in neuronal cells. This is the first report of apoptosis induction by phenanthrene-containing oxazines.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Asarum/chemistry , Brain Neoplasms/drug therapy , Neuroblastoma/drug therapy , Plant Roots/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Caspases/drug effects , Cell Line, Tumor , Cell Nucleus/drug effects , Cell Nucleus/ultrastructure , Enzyme Activation/drug effects , Humans , Molecular Structure , Phenanthrenes/chemistry , Phenanthrenes/pharmacology , X-Ray DiffractionABSTRACT
Two cassane-type furanoditerpenoids, designated caesalacetal and caesalpinetate, and a norditerpenoid designated caesalpinone were isolated from the roots of Caesalpinia decapetala var. japonica along with seven known diterpenoids. Structures were elucidated by interpretation of their spectroscopic data, and the absolute structure of caesalacetal was confirmed by X-ray crystallographic analysis. Furthermore, the structure of a previously reported furanoditerpenoid, caesaljapin, was revised as its C-4 epimer on the basis of detailed NMR spectroscopic data as well as X-ray crystallographic analysis.