Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents.

In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis (S. faecalis) ATCC 29212) and one Gram-(-) strain (Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap-Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O-ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis, MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06-0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM (8f) and 0.12 mM (8h). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.

The neuroprotective effect of eupatilin against ischemia/reperfusion-induced delayed neuronal damage in mice.

Eupatilin, a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have anti-oxidant, anti-inflammatory, anti-allergic, and anti-tumor activities. In the present study, we investigated whether eupatilin exhibits neuroprotective activities against ischemia/reperfusion-induced delayed neuronal injury in mice. Transient global cerebral ischemia was induced in mice by bilateral common carotid artery occlusion (BCCAO) for 15 min followed by reperfusion for 4 days. Eupatilin (1, 3, or 10 mg/kg, p.o.) was administered immediately after the reperfusion. Histochemical studies showed that eupatilin (10 mg/kg) increased the number of viable cells detected by Nissl staining and decreased the number of degenerating neuronal cells detected by Fluoro-Jade B staining in the hippocampal CA1 region. Western blotting indicated that eupatilin further increased the level of Akt phosphorylation at 8h after BCCAO. Furthermore, wortmannin, a phosphatidylinositol 3-kinase inhibitor, attenuated the eupatilin-induced increase of Akt phosphorylation. In addition, wortmannin completely reversed the eupatilin-induced neuroprotective effects observed at 4 days after reperfusion. These findings suggest that eupatilin is a promising therapeutic agent against global cerebral ischemia-induced neuronal damage and that its neuroprotective effects may be mediated in part by increased Akt phosphorylation.

Oroxylin A analogs exhibited strong inhibitory activities against iNOS-mediated nitric oxide (NO) production.

A number of oroxylin A analogs were prepared and evaluated for their inhibitory activities against iNOS-mediated nitric oxide (NO) production from LPS-stimulated BV2 cells. The analogs were synthesized from purchased 2'-hydroxy-4,5,6-trimethoxyacetophenone and aldehydes in 3 steps. Among the tested compounds, several analogs (3b, 3c, 3d, 3f) exhibited strong inhibitory activities. Especially, the analog with 4-nitrophenyl group (3b) showed stronger inhibitory activity (IC(50)=4.73 µM) than that of wogonin (IC(50)=7.80 µM).