Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate

Widespread pathologies such as atherosclerosis, metabolic syndrome and cancer are associated with dysregulation of sterol biosynthesis and metabolism. Cholesterol modulates the signaling pathways of neoplastic transformation and tumor progression. Lanosterol 14-alpha demethylase (cytochrome P450(51), CYP51A1) catalyzes one of the key steps in cholesterol biosynthesis. The fairly low somatic mutation frequency of CYP51A1, its druggability, as well as the possibility of interfering with cholesterol metabolism in cancer cells collectively suggest the clinical importance of CYP51A1. Here, we show that the natural flavonoid, luteolin 7,3′-disulfate, inhibits CYP51A1 activity. We also screened baicalein and luteolin, known to have antitumor activities and low toxicity, for their ability to interact with CYP51A1. The K_d values were estimated using both a surface plasmon resonance optical biosensor and spectral titration assays. Unexpectedly, in the enzymatic activity assays, only the water-soluble form of luteolin—luteolin 7,3′-disulfate—showed the ability to potently inhibit CYP51A1. Based on molecular docking, luteolin 7,3′-disulfate binding suggests blocking of the substrate access channel. However, an alternative site on the proximal surface where the redox partner binds cannot be excluded. Overall, flavonoids have the potential to inhibit the activity of human CYP51A1 and should be further explored for their cholesterol-lowering and anti-cancer activity.     

Dielectric properties of polytetrafluoroethylene films modified by direct current discharge

Dielectric characteristics of polytetrafluoroethylene (PTFE) films modified by direct current discharge at the anode and cathode have been studied as a function of frequency and temperature. It has been found that the dielectric constant increases slightly as a result of plasma treatment and weakly depends on temperature. It has been shown that the frequency dependences of conductivity at 20°C differ somewhat for the original and treated films, but the closer resemble one another at 80°C, with the difference in the critical conductivity indices becoming more significant.     

Modification of unsaturated rubbers in low-temperature plasma as a method to improve their adhesion properties

The change in the contact-surface properties of the films of unsaturated rubbers under the effect of a direct-current discharge has been investigated in case of the placement of the samples at the anode. It has been demonstrated that the modification in plasma leads to a substantial improvement in the contact properties of rubber films.