Two Novel Mouse Models of Duchenne Muscular Dystrophy with Similar Dmd Exon 51 Frameshift Mutations and Varied Phenotype Severity.

Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by an array of mutations in the dystrophin gene, with the most commonly mutated regions being exons 48-55. One of the several existing approaches to treat DMD is gene therapy, based on alternative splicing and mutant exon skipping. Testing of such therapy requires animal models that carry mutations homologous to those found in human patients.

Ursolic acid-based 24-nor- and A--24-oxy-triterpenoids.

Using methyl 2-cyano-3,4--12(13),4(23)-diene-ursolate as a starting scaffold a series of 3-oxo-24-nor-ursolate and A--ursanes holding hydroxy-, furoyloxy-, -tosyloxy- as well as aldehyde fragments at C24 that possess cytotoxic activity has been synthesised. The structures of the new ursanes were confirmed by detailed spectral data analysis. The chemoselectivity of methyl 2-cyano-3,4--12(13),4(23)-diene-ursolate oxidation involving the double bond in the A cycle was observed.

An unexpected conversion of 2E-furfurylidene-3-oxo-24-nor-allobetulin to 23-nor-allobetulins.

A series of 2E-furfurylidene-23-nor- and 24-nor-allobetulins has been synthesized by the Claisen-Schmidt condensation and conditions of their formation were studied in detail. It was found that among an expected 2E-furfurylidene-3-oxo-24-nor-allobetulin 4 two byproducts holding 3-oxo-4α-hydroxy- 5 and 3β,4α-dihydroxy- 6 substituents were formed, which could become the main products under the change of reaction time and amount of the base solution. Moreover, a conversion of individual 2E-furfurylidene-23-nor-3-oxo-4α-hydroxy- 5 into 2E-furfurylidene-23-nor-3β,4α-dihydroxy-derivative 6 under the treatment with the base solution was observed.

24-Nor-allobetulins possess strong α-glucosidase inhibitory activity.

A series of 24-nor-allobetulin derivatives holding 3β-hydroxy-, oxime, methoxyoxime, lactame and 4-bromobenzylidene substituents have been synthesized and their differences in the NMR spectra were studied in detail. It was revealed that 3-oxo-24-nor-allobetulin loses selectivity in the reaction of oximation and forms a mixture of oximes (and methoxyoximes) in contract to the related derivatives of native scaffold (that forms only -isomers). The screening of α-glucosidase inhibitory activity revealed that 24-nor-allobetulins are more active than allobetulins.

Novel Synthesized -Ethyl-Piperazinyl-Amides of C2-Substituted Oleanonic and Ursonic Acids Exhibit Cytotoxic Effects through Apoptotic Cell Death Regulation.

A series of novel hybrid chalcone N-ethyl-piperazinyl amide derivatives of oleanonic and ursonic acids were synthesized, and their cytotoxic potential was evaluated in vitro against the NCI-60 cancer cell line panel. Compounds and exhibited the highest overall anticancer activity, with GI values in some cases reaching nanomolar values. Thus, the two compounds were further assessed in detail in order to identify a possible apoptosis- and antiangiogenic-based mechanism of action induced by the assessed compounds.

Synthesis of erythrodiol C-ring derivatives and their activity against Chlamydia trachomatis.

To develop new potential agents against Chlamydia trachomatis among oleanane type triterpenoids the synthesis, spectral and X-ray analysis as well as antimicrobial screening of C-12 oxygen and nitrogen derivatives of erythrodiol is presented. The reduction of methyl 3β-acetoxy-12-oxo-oleanoate with LiAlH led to isomeric erythrodiol 12β- and 12α-hydroxy-derivatives, their stereochemistry with respect to the position of hydroxyl-group at C-12 was determined based on the multiplets splitting patterns, the magnitude of the spin-spin interaction, and NOESY interactions. Methyl 3β-acetoxy-12-oxo-oleanoate was transformed to 12E-hydroxyimino- and 12E-methoxyimino-derivatives by the interaction with NHOH∙HCl or CHONH∙HCl, respectively.

[A medicinal liver injury with an immunomodulatory drug of natural origin. Case report].

As practice shows, there are many alternative drugs that cause drug damage to the liver. A case of medicinal damage to the liver with an immunomodulatory herbal preparation Immunostimulating collection, which included St. John's wort, Elecampane, Kopeichnik, Echinacea, Licorice, Rosehip, is presented.

Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential.

The chalcone derivatives of 20-oxo-lupanes have been synthesised and screened for some types of biological activity. Ozonolysis of lupanes afforded 20-oxo-derivatives with the following condensation using different aromatic aldehydes by Claisen‒Schmidt reaction to the target compounds. The configuration of 19-[3-(pyridin-3-yl)-prop-2-en-1-one]-fragment was established by X-ray analysis.

Synthesis and antimycobacterial activity of triterpeni≿ A-ring azepanes.

A series of A-ring azepanones and azepanes derived from betulonic, oleanonic and ursonic acids was synthesized and evaluated for their in vitro antimycobacterial activities against M. tuberculosis (MTB) H37Rv and SDR-TB in the National Institute of Allergy and Infectious Diseases. Triterpenic A-azepano-28-hydroxy-derivatives were synthesized by the reduction with LiAlH of triterpenic azepanones available from the Beckmann rearrangement of the corresponding C3-oximes.

[Synthesis and cytotoxicity of allobetulin derivatives].

The synthesis and screening of antitumor activity in vitro (cytotoxicity) of various oxygen, nitrogen, sulfur and platinum-containing derivatives of allobetulin, including different arrangements of the double bonds in the A and B rings, penta- and hexacyclic ring A, 21-acetyl-20,28-epoxy-18α,19βH-ursane-isomeric cycle E, was carry out. (3R,5R)-19β,28-Epoxy-4,5-seco-18α-olean-3(5)-ozonide and 2,3-indolo-21β-acetyl-20β,28-epoxy-18α, H-19β-ursane showed significant cytotoxic activity against melanoma MeWo and Leukemia SR cells, appropriately. (3S,5S)-Diastereomer of the first compound showed no cytotoxicity.

[Synthesis and cytotoxicity of triterpenoid seven members cyclic amines].

Synthesis of 3-deoxy-3a-homo-3a-aza-derivatives of betulin and erythrodiol from betulonic and oleanonic acids was carried out. The most antineoplastic activity with a wide range of action at in vitro testing showed 3-deoxy-3a-homo-3a-aza-28-hydroxy-12(13)-oleanene, which by results of profound studying could be recommended for in vivo investigation. Its modification in the C28 position by introduction of amethoxycinnamoyl fragment led to a loss of antineoplastic activity.

[Boceprevir: new possibilities for antiviral treatment of chronic hepatitis C].

The given clinical review covers current antiviral therapy for chronic hepatitis C. Traditional antiviral therapy with pegylated interferon-alpha and ribavirin in patients with chronic hepatitis C virus genotype 1 allows a sustained virological response (SVR) to be achieved in no more than 40% of the treated patients. The practical introduction of the third component of the therapy as direct-acting antiviral agents makes it possible to substantially increase SVR, on the one hand, and to reduce treatment time, on the other hand.

[Telaprevir: new possibilities for antiviral treatment in patients with chronic hepatitis C].

The review considers the chemical structure, pharmacodynamics and pharmacokinetics of telaprevir, a new direct-acting antiviral agent, used to treat patients with chronic hepatitis C (CHC). The given data on Phase II and III clinical trials enable the authors to state the high efficacy of the drug in patients infected with hepatitis C virus type 1. The paper also provides data on the resistance of telaprevir and its drug interaction and denotes the place of the drug in the current antiviral treatment of patients with CHC.

[Synthesis and antitumor activity of betulin, erythrodiol and uvaol aminopropoxy derivatives].

The synthesis of aminopropoxy derivatives of betulin, erythrodiol, uvaol and oleantriol via cyanoethylation of triterpenoids hydroxyl groups and subsequent reduction of cyanoethyl fragments is described. High and specific in vitro antitumor activity (cytotoxicity) of 3beta,28-di-O-[3-(aminopropoxy)]lupa-20(29)-ene and 3beta-O-hydroxy-28-O-[3-(aminopropoxy)]olean-12-ene towards a wide range of human tumor cell lines is discovered. The aminopropoxy group is shown to be a new perspective pharmacophor group for design of anticancer agents on the basis of triterpenoids.

[Synthesis of triterpenoid acylates - an effective reproduction inhibitors of influenza A (H1N1) and papilloma viruses].

The synthesis of a new group of triterpenoid acylates on the basis of oleanolic, glycyrrhetic and ursolic acids and betulin is described. In studying the activity of the synthesized compounds in relation to reproduction of virus pathogens of respiratory infections 28-O-methoxycynnamoylbetulin shows high activity against influenza type A (H1N1) the selectivity index SI > 100. The high activity of 3,28-dinicotinoylbetulin against papilloma virus (strain HPV-11) was detected, the selectivity index SI was 35.

Synthesis of triterpenoid acylates: Effective reproduction inhibitors of influenza A (H1N1) and papilloma viruses.

The synthesis of a new group of triterpenoid acylates has been conducted on the basis of oleanolic, glycyrrhetic, and ursolic acids and betulin. 28--Methoxycynnamoylbetulin has been demonstrated to possess high activity against the influenza type A (H1N1) virus with the selectivity index SI > 100 while studying the activity of the synthesized compounds in relation to the reproduction of viral pathogens of respiratory infections. The high activity of 3,28-dinicotinoylbetulin against the papilloma virus (strain HPV-11) was detected with the selectivity index SI 35.

[Is it possible to train Achatina fulica using visual stimulation?].

The conditioned behavior to visual stimuli was obtained in Achatina fulica mollusk on the basis of its negative phototaxis. Directional moving of snails toward black cards was accompanied by the negative unconditioned stimulation (electric current). Learning was expressed in a statistically significant decrease in locomotor activity of animals and decrease in the rate of preference of sections with black cards.

[Synthesis of the lupane group triterpenoids and there hepatoprotective activity].

Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, and p-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor. These experimental data were in a good agreement with the computer prediction of their biological activity.

[The characteristics of progressive dementias in patients with herpetic encephalitis].

9 lethal cases of progressive dementias were analysed, both psychical and neurological disturbances characteristics on different stages of herpetic dementias were presented, a number of clinical morphological criteria of diagnosis ascertaining was described. It was determined that progressive dementias turned out to be one of the clinical forms of chronic CNS herpetic infection which was conditioned by prolonged persistence and activation of herpes simplex virus in brain tissue.

[Health disorders in workers of the fish processing industry].

The contributors propose a study of the labour conditions (microclimate, work load and intensity) in processing of dried yellowfin fish, describe results of the psycho-physiological and clinical studies, including medical examinations, epicutaneous testing, ventilation capacity of the lungs and peripheral blood laboratory studies. It was established that the technological processes of drying yellowfin fish exhibited exposure to the biological factors causing irritations and sensibilization of the skin fraught with occupational diseases (dermatitis) and respiratory disorders (allergic rhinopathy and the pre-asthma syndrome).