Isolation, identification, and biological evaluation of HIF-1-modulating compounds from Brazilian green propolis.

The tumor microenvironment is characterized by hypoxia, low-nutrient levels, and acidosis. A natural product chemistry-based approach was used to discover small molecules that modulate adaptive responses to a hypoxic microenvironment through the hypoxia-inducible factor (HIF)-1 signaling pathways. Five compounds, such as baccharin (3), beturetol (4), kaempferide (5), isosakuranetin (6), and drupanin (9), that modulate HIF-1-dependent luciferase activity were identified from Brazilian green propolis using reporter assay. Compounds 3, 9 and 5 reduced HIF-1-dependent luciferase activity. The cinnamic acid derivatives 3 and 9 significantly inhibited expression of the HIF-1α protein and HIF-1 downstream target genes such as glucose transporter 1, hexokinase 2, and vascular endothelial growth factor A. They also exhibited significant anti-angiogenic effects in the chick chorioallantoic membrane (CAM) assay at doses of 300 ng/CAM. On the other hand, flavonoids 4 and 6 induced HIF-1-dependent luciferase activity and expression of HIF-1 target genes under hypoxia. The contents (g/100g extract) of the HIF-1-modulating compounds in whole propolis ethanol extracts were also determined based on liquid chromatography-electrospray ionization mass spectrometry as 1.6 (3), 14.2 (4), 4.0 (5), 0.7 (6), and 0.7 (9), respectively. These small molecules screened from Brazilian green propolis may be useful as lead compounds for the development of novel therapies against ischemic cardiovascular disease and cancer based on their ability to induce or inhibit HIF-1 activity, respectively.

Three new isoflavanones from Erythrina costaricensis.

Three new isoflavanones, 5,7,3'-trihydroxy-4'-methoxy-6,5'-di(gamma, gamma-dimethylallyl)-isoflavanone (1), 5,3'-dihydroxy-4'-methoxy-5'-gamma,gamma-dimethylallyl-2'',2''-dimethylpyrano[5,6 : 6,7]isoflavanone (2) and 5,3'-dihydroxy-2'',2''-dimethylpyrano[5,6 : 6,7]-2''',2'''-dimethylpyrano[5,6 : 5,4]isoflavanone (3), along with two known isoflavonoids, cristacarpin and euchrenone b(10), were isolated from the stems of Erythrina costaricensis. Their structures were established on the basis of spectroscopic evidence. Compound 3 is a rare isoflavanone possessing two 2,2-dimethylpyran moieties. Among the new isoflavanones, compound 1 showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus.

Two new isoflavanones from Erythrina costaricensis.

Two new isoflavanones, 5,3'-dihydroxy-4'-methoxy-5'-(3-methyl-1,3-butadienyl)-2'',2''-dimethylpyrano[5,6:6,7]isoflavanone (1) and 5,3'-dihydroxy-5'-(3-hydroxy-3-methyl-1-butenyl)-4'-methoxy-2'',2''-dimethylpyrano[5,6:6,7]isoflavanone (2), together with two known isoflavonoids, cristacarpin, and euchrenone b10, were isolated from the stems of Erythrina costaricensis. Their structures were established on the basis of spectroscopic evidence. These new compounds are rare isoflavanones, possessing both a 2,2-dimethylpyran substituent and a prenyl analog. The antibacterial activities of 1 and 2 against the methicillin-resistant Staphylococcus aureus were examined.

A new Erythrina alkaloid from Erythrina herbacea.

A new Erythrina alkaloid, 10-hydroxy-11-oxoerysotrine (1), has been isolated from the flowers of Erythrina herbacea together with five known compounds: erytharbine (2), 10,11-dioxoerysotrine (3), erythrartine (4), erysotramidine (5) and erysotrine-N-oxide (6). The structure of the new compound was elucidated on the basis of its spectral data, including 2-D NMR and mass (MS) spectra. The new compound is a rare C-10 oxygenated Erythrina alkaloid. The antioxidant activities of the isolated compounds 1-6 were evaluated by scavenging with peroxynitrite.