Evaluation of 3- and 4-Phenoxybenzamides as Selective Inhibitors of the Mono-ADP-Ribosyltransferase PARP10

Intracellular ADP-ribosyltransferases catalyze mono- and poly-ADP-ribosylation and affect a broad range of biological processes. The mono-ADP-ribosyltransferase PARP10 is involved in signaling and DNA repair. Previous studies identified OUL35 as a selective, cell permeable inhibitor of PARP10. We have further explored the chemical space of OUL35 by synthesizing and investigating structurally related analogs. Key synthetic steps were metal-catalyzed cross-couplings and functional group modifications. We identified 4-(4-cyanophenoxy)benzamide and 3-(4-carbamoylphenoxy)benzamide as PARP10 inhibitors with distinct selectivities. Both compounds were cell permeable and interfered with PARP10 toxicity. Moreover, both revealed some inhibition of PARP2 but not PARP1, unlike clinically used PARP inhibitors, which typically inhibit both enzymes. Using crystallography and molecular modeling the binding of the compounds to different ADP-ribosyltransferases was explored regarding selectivity. Together, these studies define additional compounds that interfere with PARP10 function and thus expand our repertoire of inhibitors to further optimize selectivity and potency.     

Pharmacognostic Evaluation and HPLC–PDA and HS–SPME/GC–MS Metabolomic Profiling of Eleutherococcus senticosus Fruits

Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. is a medicinal plant used in Traditional Chinese Medicine (TCM) for thousands of years. However, due to the overexploitation, this species is considered to be endangered and is included in the Red List, e.g., in the Republic of Korea. Therefore, a new source of this important plant in Europe is needed. The aim of this study was to develop pharmacognostic and phytochemical parameters of the fruits. The content of polyphenols (eleutherosides B, E, E1) and phenolic acids in the different parts of the fruits, as well as tocopherols, fatty acids in the oil, and volatile constituents were studied by the means of chromatographic techniques [HPLC with Photodiode-Array Detection (PDA), headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry (HS–SPME/GC–MS)]. To the best of our knowledge, no information is available on the content of eleutherosides and phenolic acids in the pericarp and seeds. The highest sum of eleutheroside B and E was detected in the whole fruits (1.4 mg/g), next in the pericarp (1.23 mg/g) and the seeds (0.85 mg/g). Amongst chlorogenic acid derivatives (3-CQA, 4-CQA, 5-CQA), 3-CQA was predominant in the whole fruits (1.08 mg/g), next in the pericarp (0.66 mg/g), and the seeds (0.076 mg/g). The oil was rich in linoleic acid (C18:3 (n-3), 18.24%), ursolic acid (35.72 mg/g), and α-tocopherol (8.36 mg/g). The presence of druses and yellow oil droplets in the inner zone of the mesocarp and chromoplasts in the outer zone can be used as anatomical markers. These studies provide a phytochemical proof for accumulation of polyphenols mainly in the pericarp, and these structures may be taken into consideration as their source subjected to extraction to obtain polyphenol-rich extracts.     

Evaluation of the Antioxidant,Cytoprotective and Antityrosinase Effects of Schisandra chinensis Extracts and Their Applicability in Skin Care Product

Plant extracts have been widely used for skin care for many centuries, and nowadays, they are commonly applied for the development and enrichment of new cosmetic preparations. The present study aimed the assessment of the biological activity of aqueous Schisandra chinensis extracts as a potential ingredient of skin care products. The aspects studied involved the ability to neutralize free radicals, impact on viability and metabolism of keratinocytes, as well as tyrosinase inhibitory potential. Our study showed that aqueous S. chinensis extracts have a positive effect on keratinocyte growth and have high antioxidant potential and strong tyrosinase inhibitory activity. UPLC-MS analysis revealed that three groups of phenolic compounds were predominant in the analyzed extract, including lignans, phenolic acids and flavonoids and protocatechiuc and p-coumaryl quinic acids were predominant. Moreover, microwave-assisted extraction, followed by heat reflux extraction, was the most effective for extracting polyphenols. Furthermore, a prototypical natural body washes gel formulation containing the previously prepared extracts was developed. The irritation potential and viscosity were assessed for each of the formulations. The study demonstrated that the addition of these extracts to body wash gel formulations has a positive effect on their quality and may contribute to a decrease in skin irritation. In summary, S. chinensis aqueous extracts can be seen as an innovative ingredient useful in the cosmetic and pharmaceutical industry.     

Picard-Vessiot theory for real fields

The existence of a Picard-Vessiot extension for a homogeneous linear differential equation has been established when the differential field over which the equation is defined has an algebraically closed field of constants. In this paper, we prove the existence of a Picard-Vessiot extension for a homogeneous linear differential equation defined over a real differential field K with real closed field of constants. We give an adequate definition of the differential Galois group of a Picard-Vessiot extension of a real differential field with real closed field of constants and we prove a Galois correspondence theorem for such a Picard-Vessiot extension.     

Filamentary cavity formation in poly(methyl methacrylate) by single femtosecond pulse

A single femtosecond laser pulse creates a filamentary structural change along the optical axis inside bulk poly(methyl methacrylate). The filamentary structural change was revealed to be a cylindrical cavity based on scanning electron microscope examination, the presence of capillary action, and analysis of diffraction by an embedded diffraction grating. The cavity had a diameter of 0.8 μm and a length of 125 μm. PACS 42.65.Jx; 42.70.Jk     

Fractional quantization of Hall resistance as a consequence of mesoscopic feedback

A nonlinear single-particle model is introduced, which captures the characteristic of systems in the quantum Hall regime. The model involves the magnetic Schrödinger equation with spatially variable magnetic flux density. The distribution of flux is prescribed via the postulates of the mesoscopic mechanics (MeM) introduced in my previous articles (cf. [9, 10]). The model is found to imply exact integer and fractional quantitzation of the Hall conductance. In fact, Hall resistance is found to be R _H = (h/e ²)(M/N) at the filling factor value N/M. The assumed geometry of the Hall plate is rectangular. Special properties of the magnetic Schrödinger equation with the mesoscopic feedback loop allow us to demonstrate quantization of Hall resistance as a direct consequence of charge and flux quantization. I believe results presented here shed light at the overall status of the MeM in quantum physics, confirming its validity.     

Facility for proton radiotherapy of eye cancer at IFJ PAN in Krakow

In the Henryk Niewodniczański Institute of Nuclear Physics of the Polish Academy of Science in Krakow (IFJ PAN), Poland, in cooperation with the Department of Ophthalmology and Ophthalmic Oncology of the Collegium Medicum, Jagiellonian University and the Centre of Oncology of the Maria Sk?odowska-Curie Memorial Institute Krakow Branch, is running the project of designing and operating a proton ocular radiotherapy facility in which the 60 MeV proton beam accelerated in the AIC-144 isochronous cyclotron of IFJ PAN is applied. The facility will be able to satisfy national needs of ocular melanoma therapy in Poland (about 100 cases per year).     

Chelating Sorbents Prepared by the Modification of Silica Gel, Lichroprep RP-8 and Lichroprep RP-18 with Calcon and Their Application in the Analysis of Some Metal Ions

 Two new chelating sorbents for metal ions were prepared by the impregnation of chemically modified silicas LiChroprep RP-8 and RP-18 with ion pairs composed of the cation of Aliquat 336 and the anion of Calcon. The sorbents were compared with an analogous sorbent with a plain silica carrier containing the same ion pairs. A hypothesis for binding this ion pair by the surfaces of the applied carriers was presented. A higher stability of the two sorbents in comparison with that of the plain silica chelating sorbent was demonstrated. The sorbents obtained were applied for chromatographic separations of some chosen mixtures of some metal ions and for additional purification of aqueous solutions of alkali metals from trace amounts of heavy metals. The multiple use of the sorbents based on RP-8 and RP-18 in sorption–desorption processes of metal ions without deterioration of their sorption capacities was demonstrated. Received March 8, 2000. Revision March 5, 2001.     

Effectiveness of Volatile Natural Deep Eutectic Solvents (VNADESs) for the Green Extraction of Chelidonium majus Isoquinoline Alkaloids

The Chelidonium majus plant is rich in biologically active isoquinoline alkaloids. These alkaline polar compounds are isolated from raw materials with the use of acidified water or methanol; next, after alkalisation of the extract, they are extracted using chloroform or dichloromethane. This procedure requires the use of toxic solvents. The present study assessed the possibility of using volatile natural deep eutectic solvents (VNADESs) for the efficient and environmentally friendly extraction of Chelidonium alkaloids. The roots and herb of the plant were subjected three times to extraction with various menthol, thymol, and camphor mixtures and with water and methanol (acidified and nonacidified). It has been shown that alkaloids can be efficiently isolated using menthol–camphor and menthol–thymol mixtures. In comparison with the extraction with acidified methanol, the use of appropriate VNADESs formulations yielded higher amounts of protopine (by 16%), chelidonine (35%), berberine (76%), chelerythrine (12%), and coptisine (180%). Sanguinarine extraction efficiency was at the same level. Additionally, the values of the contact angles of the raw materials treated with the tested solvents were assessed, and higher wetting dynamics were observed in the case of VNADESs when compared with water. These results suggest that VNADESs can be used for the efficient and environmentally friendly extraction of Chelidonium alkaloids.