Медицинская химия

We described the synthesis of carboxamide derivatives designed as novel simplified imatinib analogues and their antiproliferative and anti-inflammatory activities. Compound 2c showed a unique conformation determined by X-ray diffraction and by NMR 1H and displayed antiproliferative potency in the same magnitude order than the standard imatinib. Compounds 6-10 were prepared by structural modification in carboxamide 2c, and with exception of derivative 10, they were inactive as antiproliferative agent. However, these compounds showed same anti-inflammatory potency than imatinib, standing out carboxamide 9 that was six time more potent as TNF-α inhibitor production.

Drug delivery systems must overcome a series of biological barriers to escort therapeutical agents to specific pathological site. These include both extracellular barriers and intracellular barriers. To overcome extracellular barriers, the vehicles should have high stability and prolonged circulation time in the blood stream, and sufficient accumulation in disease site. Intracellular barriers are the subsequent barrier that determines successful drug or gene delivery, including effective cellular internalization, endosomal escape, and controllable release. Comprehensive consideration of both extracellular and intracellular barriers to targeted drug and gene delivery is critically important. Nanoparticles (NPs) based drug and gene delivery systems exhibit potential ability to overcome the biological barriers, due to their structures can be tailored to address those barriers such as release the therapeutic agents in the desired site. In this review, we will focus on recent exciting advances in designing redox sensitive nanoparticles for intracellular drug delivery. Those redox sensitive NPs are particularly concentrated on recent emerging NPs with disulfide bond linked sheddable shell like PEG. 

Researchers are in constant search for the ideal implant surface condition in an attempt to improve osseointegration and to increase bone-to-implant contact. Although various techniques such as physicochemical and morphologic modification, have been proposed, they are still incapable of ensuring predictable results and guaranteed success. In recent years, investigators have also attempted to improve bone formation around implants via using biochemical modification. Various kinds of biomolecules have been introduced to endow the titanium surfaces bioactivities because of their certain bone-growth promoting capabilities. A review of the research progress is given in this paper concerning the biochemical modification of the implant surface.

We hereby present a protocol for Native Chromatin Immunoprecipitation (NChIP) on brain tissue. Maintaining the chromatin in it’s native state, as opposed to cross-linkage by formaldehyde, and using magnetic beads (instead of sepharose beads) facilitates a very sensitive and specific immunoprecipitation (up to 98% enrichment relative to input). Performing qPCR on acetylated H4 precipitated DNA, we found a 12-fold enrichment of the active actin gene compared to the inactive globin gene. Furthermore, very small inter assay variations were found across individual animals. The high sensitivity and specificity of the present protocol circumvents the need for large tissue samples, which is often a limiting factor when working with brain tissue.

Only the flowers of lavender (Lavandula angustifolia) are utilized for the medical purposes. The aim of the current study was to compare the chemical composition, concentrations of flavonoids and sesquiterpene acids in the leafy stems in two varieties of lavender oils the ‘Blue River’ (BR) and the ‘Ellegance Purple’ (EP). Their biological activity against four pathogenic bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis was study. The main constituents were borneol (13.8-12.4%), and caryophyllene oxide (8.0- 8.7%). Total flavonoids content were similar in both plants, from 341 to 352 mg/100 g. The valerenic acid was from 1.08 to 0.81 mg/100 g in BR and EP, respectively. The acetoxyvalerenic acid was from 45.9 to 14.0 mg/100 g, respectively. The highest increase of S. aureus bacteria was inhibited by the activity of the essential oils from both varieties. The less effect of inhibition was noticed for Escherichia coli for both plants.

Maesobotrya barteri (Baill), belonging to the family EUPHORBIACEAE, is a medicinal plant growing widely in tropical Africa. The Aerial plant parts of Maesobotrya barteri (Bail) were collected fresh from Orokam, Ogbadibo local Government of Benue State, Nigeria in July, 2013. Taxonomical identification was done by Mallam Musa Abdullahi at the Herbarium unit of Biological sciences Department, ABU, Zaria, Nigeria. Pulverized aerial parts of Maesobotrya barteri (960g) was exhaustively extracted successively using petroleum ether, chloroform, ethyl acetate and methanol and concentrated in the rotary evaporator at 40°C. The ethyl acetate fraction having the highest activity against test microbes from preliminary crude microbial screenings was subjected to phytochemical studies, antimicrobial analysis and column chromatography (CC). The column chromatography yielded fraction EN, which was further purified using preparative thin layer chromatography to give EN1. The structure of the isolated compound was established using 1-D NMR and 2-D NMR spectroscopic analysis and by direct comparism with data reported in literature was confirmed to be β-amyrin. The bioactivity of this compound was carried out using some clinical pathogens and the activity compared with standard drugs and this was found to be comparable with the standard drug.

Altered genes that play a driving role in cancer development can often serve as specific diagnostic markers, criteria of molecular classification and therefore potential therapeutic targets. Serine protease inhibitor Kazal type 1 (SPINK1), also known as pancreatic secretory trypsin inhibitor or tumor-associated trypsin inhibitor, encodes a 56 amino acid secreted peptide, and its normal function is thought to be the inhibition of serine proteases such as trypsin. Recent studies have indicated marked overexpression of SPINK1 defines an aggressive molecular subtype of ETS (erythroblastosis virus E26 transformation-specific) fusion-negative prostate cancer ((PCa) patients. SPINK1 may act as an autocrine growth factor and promotes PCa growth and invasion. Most recently, we suggested that SPINK1 induces epithelial-mesenchymal transition (EMT) through EGFR signaling pathway in PCa. The association between SPINK1 overexpression and poor prognosis in PCa has been reported. Notably, SPINK1 might be a novel extracellular therapeutic target in a subset of high-grade PCa patients. In this review, we will summarize the current understanding of SPINK1 involving its role in PCa biology, association with prognosis as well as perspective in therapy from the pathologist's point of view.