7-Hydroxyflavonol

Small molecule inhibitors of the HPV16-E6 interaction with caspase 8.[Pubmed:22300659]

Bioorg Med Chem Lett. 2012 Mar 1;22(5):2125-9.

High-risk strains of human papillomaviruses (HPVs) cause nearly all cases of cervical cancer as well as a growing number of head and neck cancers. The oncogenicity of these viruses can be attributed to the activities of their two primary oncoproteins, E6 and E7. The E6 protein has among its functions the ability to prevent apoptosis of infected cells through its binding to FADD and caspase 8. A small molecule library was screened for candidates that could inhibit E6 binding to FADD and caspase 8. Flavonols were found to possess this activity with the rank order of myricetin>morin>quercetin>kaempferol=galangin>>(apigenin, 7-Hydroxyflavonol, rhamnetin, isorhamnetin, geraldol, datiscetin, fisetin, 6-hydroxyflavonol). Counter screening, where the ability of these chosen flavonols to inhibit caspase 8 binding to itself was assessed, demonstrated that myricetin, morin and quercetin inhibited GST-E6 and His-caspase 8 binding in a specific manner. The structure-activity relationships suggested by these data are unique and do not match prior reports on flavonols in the literature for a variety of anticancer assays.

On the antioxidant properties of three synthetic flavonols.[Pubmed:17294818]

Pharmazie. 2007 Jan;62(1):72-6.

The antioxidant properties of a series of synthetic and natural flavonoids towards the oxygenated species superoxide radical anion (*O2-) enzimatically generated, were evaluated. 7-Hydroxyflavonol, 7,3'-dihydroxyflavonol and 3'-hydroxyflavonol were synthesised, with a systematic variation of the OH substitution on positions C3, C7, C3'and C4', and their respective antioxidative abilities compared to those of the already characterised natural flavonoids quercetin, kaempferol and rutin. The efficiency of *O2- deactivation by the flavonoids does not correlate with their respective determined oxidation potentials, suggesting that the pure one-electron-transfer-mechanism of *O2 quenching could not be the main scavenging process involved. Experimental evidence demonstrated that the possible inhibition of the *O2(-)-generator enzymatic system by the flavonoids must be disregarded as a possible indirect cause for the inhibition of the oxidative species. One possible mechanism for the inhibition of *O2-, highly dependent on the substitution pattern of the flavonoid, may be the generation of hydroperoxides or dioxetanes as oxidation products, as already postulated for other biologically relevant compounds. The simultaneous OH-substitution on positions C3 and C7 of the flavonoid skeleton plays a definitive role in the enhancement of the *O2- inhibitory effect. The replacement of OH by a O-rutinosyl group on position C7 suppresses at all that effect, whereas the absence of an OH group in position 7 significantly reduces the antioxidative power. Finally, the presence of OH groups on positions 3'and 4' does not produce any determinant effect in the antioxidative behaviour of the flavonoids.