Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors

Acetylcholinesterase (AChE) is one of the classical targets in the treatment of Alzheimer’s disease (AD). Inhibition of AChE slows down the hydrolysis of acetycholine and increases choline levels, improving the cognitive function. The achieved success of plant-based natural drugs acting as AChE inhibitors, such as galantamine (GAL) from Galanthus genus and huperzine A from Huperzia serrate (approved drug in China), in the treatment of AD, and the fact that natural compounds (NCs) are considered as safer and less toxic compared to synthetic drugs, led us to screen the available NCs (almost 150,000) in the ZINC12 database for AChE inhibitory activity. The compounds were screened virtually by molecular docking, filtered for suitable ADME properties, and 32 ligands from 23 structural groups were selected. The stability of the complexes was estimated via 1 μs molecular dynamics simulation. Ten compounds formed stable complexes with the enzyme and had a vendor and a reasonable price per mg. They were tested for AChE inhibitory and antioxidant activity. Five compounds showed weak AChE inhibition and three of them exhibited high antioxidant activity.     

Hydrogels based on polycarboxylic acid-agar-agar complexes

IR spectroscopy and viscometry data have shown that poly(acrylic acid) and poly(methacrylic acid) form complexes with agar-agar in aqueous solutions as they do with other polysaccharides. The polyacid-agar-agar complexes are typical hydrogels. The swelling index of hydrogels based on the poly(methacrylic acid)-agar-agar complex has been found to be markedly lower than that of poly(acrylic acid)-agaragar complex. The hydrogels based on the complex of cross-linked poly(acrylic acid) with agar-agar can be of practical interest as polymeric carriers for drugs.     

Camphane-based aminophosphine ligands for Pd-catalyzed asymmetric allylic alkylation

A practical synthesis of new chiral aminophosphine ligands based on the camphane scaffold bearing alkoxy groups was accomplished. The application of these ligands in the Pd-catalyzed allylic alkylation of (E)-1,3-diphenyl-2-propenyl acetate proceeded with excellent conversions and ee’s of up to 91%. Variation of the alkoxy substituents did not substantially influence the catalytic performance.     

Simulation of chemical metabolism for fate and hazard assessment. I. Approach for simulating metabolism

Information regarding the metabolism of xenobiotic chemicals plays a central role in regulatory risk assessments. In regulatory programmes where metabolism studies are required, the studies of metabolic pathways are often incomplete and the identification of activated metabolites and important degradation products are limited by analytical methods. Because so many more new chemicals are being produced than can be assessed for potential hazards, setting assessment priorities among the thousands of untested chemicals requires methods for predictive hazard identification which can be derived directly from chemical structure and their likely metabolites. In a series of papers we are sharing our experience in the computerized management of metabolic data and the development of simulators of metabolism for predicting the environmental fate and (eco)toxicity of chemicals. The first paper of the series presents a knowledge-based formalism for the computer simulation of non-intermediary metabolism for untested chemicals, with an emphasis on qualitative and quantitative aspects of modelling metabolism.     

Electrochemical production, characterization, and application of MWCNTs

The subject of this study is production of carbon nanotubes (CNTs) using an original procedure of reduction of lithium molten salts onto graphite cathode; their structural characterization and application as support material for electrocatalysts aimed for hydrogen evolution. As-produced CNTs were characterized by means of scanning and transmission electron microscopy (SEM and TEM), Raman spectroscopy, and thermogravimetric and differential thermal analysis (DTA). SEM and TEM images have shown that nanotubes are mostly of curved shape with length of 1–20 μm and diameter of 20–40 nm. Raman peaks indicate that the crystallinity of produced nanotubes is rather low. The obtained results suggest that formed product contains up to 80 % multiwalled carbon nanotubes (MWCNTs), while the rest being non-reacted graphite and fullerenes. DTA curves show that combustion process of the nanotubes takes place in two stages, i.e., at 450 and 720 °C. At the lower temperature, combustion of MWCNTs occurs, while at higher one, fullerenes and non-reacted graphite particles burn. As-produced MWCNTs were used as electrocatalyst’s support materials and their performance was compared with that of traditional carbon support material Vulcan XC-72. MWNTs have shown almost twice higher real surface area, and electrocatalyst deposited on them showed better catalytic activity than corresponding one deposited on Vulcan XC-72.     

Peak effect in polycrystalline vortex matter

We report a study of the peak-effect phase diagram of a strongly disordered type-II superconductor V-21 at. %Ti using ac magnetic susceptibility and small-angle neutron scattering (SANS). In this system, the peak effect appears only at fields higher than 3.4 T. The sample is characterized by strong atomic disorder. Vortex states with field-cooled thermal histories show that both deep in the mixed state, as well as close to the peak effect, there exist no long-range orientationally ordered vortex lattices. The SANS scattering radial widths reveal vortex states ordered in the sub-mum scale. We conjecture that the peak effect in this system is a remnant of the Bragg glass disordering transition, but occurs on submicron length scales due to the presence of strong atomic disorder on larger length scales.     

Functional Polyion Complex Micelles for Potential Targeted Hydrophobic Drug Delivery

Polyion complex (PIC) micelles have gained an increasing interest, mainly as promising nano-vehicles for the delivery of various hydrophilic charged (macro)molecules such as DNA or drugs to the body. The aim of the present study is to construct novel functional PIC micelles bearing cell targeting ligands on the surface and to evaluate the possibility of a hydrophobic drug encapsulation. Initially, a pair of functional oppositely charged peptide-based hybrid diblock copolymers were synthesized and characterized. The copolymers spontaneously co-assembled in water into nanosized PIC micelles comprising a core of a polyelectrolyte complex between poly(L-aspartic acid) and poly(L-lysine) and a biocompatible mixed shell of disaccharide-modified poly(ethylene glycol) and poly(2-hydroxyethyl methacrylate). Depending on the molar ratio between the oppositely charged groups, PIC micelles varying in surface charge were obtained and loaded with the natural hydrophobic drug curcumin. PIC micelles’ drug loading efficiency, in vitro drug release profiles and antioxidant activity were evaluated. The preliminary results indicate that PIC micelles can be successfully used as carriers of hydrophobic drugs, thus expanding their potential application in nanomedicine.     

Sharp bounds for the extreme zeros of classical orthogonal polynomials

Bounds for the extreme zeros of the classical orthogonal polynomials are obtained by a surprisingly simple method. Nevertheless, it turns out that, in most cases, the estimates obtained in this note are better than the best limits known in the literature.     

Gamma Vibrational Bands and Chiral Doublet Bands in A≈100 Neutron-rich Nuclei

The level structures of neutron-rich ~(105)Mo,~(106)Mo,~(108)Mo and 110Ru nuclei in A≈100 region have been carefully investigated by coincidence measurements of the prompt γ-rays populated in the spontaneous fission of ~(252)Cf with the Gammasphere detector array.In 105Mo,one-phonon K =9/2 and two-phonon K=13/2 γ-vibrational bands have been identified.In ~(108)Mo,one-phonon γ-vibrational band is expanded and two-phonon γ-vibrational band has been identified.Two similar sets of bands in ~(106)Mo and ~(110)Ru are observed to high spins,which have been proposed as the soft chiral γ-vibrational bands.The characteristics for these γ-vibrational bands and chiral doublet bands have been discussed.     

Asymptotics of zeros of polynomials arising from rational integrals

We prove that the zeros of the polynomials Pm(a) of degree m, defined by Boros and Moll via