benzofurans and oxetane

Brine shrimp lethality test (BST)-guided fractionation of a methanol extract of the roots of Melia azedarach resulted in the isolation of two new limonoids, 9alpha-hydroxy-12alpha-acetoxyfraxinellone (1) and 7,14-epoxy-azedarachin B (2), together with the known compounds, 12alpha-hydroxyfraxinellone (4), 9alpha-hydroxyfraxinellone (5), azedarachin B (6), and neoazedarachin B (7). The structures of 1 and 2 were elucidated by analysis of spectroscopic data and comparison of their NMR data with those of the known compounds. Compounds 1, 2 and 4-7 exhibited significant activity in the BST, in particular, azedarachin B (6) showed remarkable BST activity with an LC(50) value of 0.0098 microM.

Topics: Animals; Artemia; Benzofurans; Biological Assay; Ethers, Cyclic; Limonins; Magnetic Resonance Spectroscopy; Melia azedarach; Methanol; Molecular Structure; Plant Roots; Plants, Medicinal; Steroids

The effects of dietary administration of equimolar doses (5 mmol/kg body wt per day) of trimethylene oxide, trimethylene sulfide, coumaran, benzofuran, indole, and indole-3-carbinol on the activities of microsomal epoxide hydrolase and several other xenobiotic metabolizing enzymes were measured in the liver of female CD-1 mouse. Every compound, with the exception of indole, caused a significant increase (P less than 0.01) of the styrene oxide epoxide hydrolase activity over controls in hepatic microsomes. These results indicate that the enzyme activity is elevated in vivo by several heterocyclic compounds with strained bond angles to a nucleophilic hetero-atom. In addition, the ability of sulfur-containing trimethylene sulfide and nitrogen-containing indole-3-carbinol to elevate the enzyme activity indicates that the heterocyclic oxygen atom is not an absolute requirement for this effect. Data from the other xenobiotic metabolizing enzymes indicate that trimethylene oxide and trimethylene sulfide enhance the epoxide hydrolase activity rather specifically, while not affecting the activities of the other enzymes measured. While the oxygen-containing coumaran and benzofuran both increased the NADH: quinone reductase activity in hepatic cytosol, the nitrogen-containing indole and indole-3-carbinol did not. This indicated a specific requirement for the oxygen atom in elevating the quinone reductase activity, which was not the case for the elevation of microsomal epoxide hydrolase activity.

Topics: Animals; Benzofurans; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Epoxide Hydrolases; Ethers, Cyclic; Female; Glutathione Transferase; Heterocyclic Compounds; Indoles; Mice; Mice, Inbred Strains; Microsomes, Liver; Quinone Reductases; Structure-Activity Relationship