Asaroidoxazines from the Roots of Asarum asaroides Induce Apoptosis in Human Neuroblastoma Cells

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.

Isolation of Fluorescent Benzoxazines with Neuroprotective Activity from the Olive Weevil Pimelocerus perforatus

“…The final DMSO concentration in each well was 0.1% in the medium. After 24 h of culture, the cell viability was evaluated using Cell Counting Kit-8 (DOJINDO Laboratories), as previously described. , All experiments were performed in quadruplicate. The results are expressed as the means ± SD of the percentage of the treated cultures compared with those of the untreated cells.…”

Triterpenoid Saponins from the Fruits of Symplocos lucida as β‐Glucuronidase Inhibitors

“…[6,7] However, very few studies have identified the constituents in the fruits of this plant. In the course of our investigations on biologically active compounds, [8,9] we found that the methanolic extract of S. lucida fruits exhibited E. coli β-glucuronidase inhibitory activity (66 % inhibition at 1 mg/mL). The investigation of the extract resulted in the isolation of a new compound designated kurokisaponin (1) and five known triterpenoid saponins 2-6 (Figure 1).…”

Redox Modifications in the Biosynthesis of Alchivemycin A Enable the Formation of Its Key Pharmacophore

“…This TDO ring is rarely found in natural products. The limited examples containing the TDO-like moiety include asaroidoxazines and azocinyl morpholinone alkaloids isolated from a plant ( Asarum asaroides ) and red seaweed ( Gracilaria opuntia ), respectively, , and a semisynthetic cephalosporin derivative that is a promising drug candidate against Mycobacterium tuberculosis (Figure ). …”

“…The limited examples containing the TDO-like moiety include asaroidoxazines and azocinyl morpholinone alkaloids isolated from a plant (Asarum asaroides) and red seaweed (Gracilaria opuntia), respectively, 2,3 and a semisynthetic cephalosporin derivative that is a promising drug candidate against Mycobacterium tuberculosis (Figure 1). 4 Because of its potent bioactivity and complicated structure, several studies have investigated the chemical synthesis of 1.…”