ABSTRACT
Ultrasonic melt treatment (UST) was applied to Al-7Si-2Cu-1Mg melt at various temperatures of 620, 650, 700 and 785 °C. MgAl2O4 particles which were often found to be densely populated along oxide films, became effectively dispersed and well-wetted by UST. Transmission electron microscopy work combined with crystallography analysis clearly indicates that MgAl2O4 particles can act as α-Al nucleation site with the aid of UST. However, with UST, grain refinement occurred only at temperature of 620 °C and the grain size increased from 97 to 351 µm with increase of melt temperature to 785 °C for UST. In quantitative analysis of grain size and MgAl2O4 particle diameter, it was found that ultrasonic de-agglomeration decreased mean particle size of the MgAl2O4 particles, significantly reducing size from 1.2 to 0.4 µm when temperature increased from 620 to 785 °C. Such a size reduction with increased number of MgAl2O4 particles does not always guarantee grain refinement. Thus, in this work, detailed condition for achieving grain refinement by UST is discussed based on quantitative measurement. Furthermore, we tried to suggest the most valid grain refinement mechanism among the known mechanisms by investigation of the relationship between grain size and particle size with variation of melt temperature.
ABSTRACT
Five bichalcones (5-1 ~ 5-4, 9) were prepared by the reaction of biphenyl-4,4'-dicarbaldehyde (4) and 4,4'-dioxybenzaldehyde (8) with the respective acetophenone analogs via Claisen-Schmidt condensation and were then fully identified by 1H-NMR, (13)C-NMR and mass analyses.
Subject(s)
Chalcones/chemistry , Chalcones/chemical synthesis , Chalcones/pharmacology , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Previously, a synthetic biflavone having a C-C (6-6") linkage ([6,6"]biflavone, BF6-6) was shown to possess considerable anti-inflammatory activity. The present investigation was conducted to develop more active anti-inflammatory biflavonoids having unique mechanisms of action based on the BF6-6 molecule. For this purpose, 5,7-dihydroxy[6,6"]biflavone (G168) was synthesized using Suzuki-Miyaura C-C cross coupling reaction. The anti-inflammatory activities of G168 were then examined on lipopolysaccharide-treated RAW 264.7 cells, carrageenan-induced paw edema and acetic acid-induced writhing in mice. It was found that G168 showed much stronger inhibition against cyclooxygenase-2-mediated PGE2 production than the original molecule, BF6-6. It also demonstrated inhibitory activity against inducible nitric oxide synthase (iNOS)-mediated NO production at least partly by the down-regulation of iNOS. Furthermore, G168, administered intraperitoneally at a dosage of 1-5 mg/kg, showed a potent in vivo anti-inflammatory activity on carrageenan-induced paw edema and analgesic activity on acetic acid-induced writhing in mice. Therefore, the newly synthesized biflavonoid, G168, may be used as a synthetic lead for new anti-inflammatory drug development.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Biflavonoids/pharmacology , Inflammation/drug therapy , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/chemical synthesis , Biflavonoids/administration & dosage , Biflavonoids/chemical synthesis , Cell Line , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/metabolism , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/pharmacology , Dinoprostone/biosynthesis , Disease Models, Animal , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Inflammation/physiopathology , Lipopolysaccharides , Male , Mice , Mice, Inbred ICR , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/antagonists & inhibitorsABSTRACT
A number of 8-arylflavones have been synthesized as congeners of wogonin and evaluated for their inhibitory activities of PGE2 production. 8-Arylflavones were obtained from commercially available chrysin via two different synthetic pathways. Most 8-arylflavones exhibited much reduced inhibitory activities against COX-2 catalyzed PGE2 production compared to that of wogonin. Functional group replacement at the 8-position of wogonin from methoxy to aryl group caused loss of inhibitory activity. Our present results imply that the functional group at the 8-position of flavones seems to play very important roles for bioactivity.
