ABSTRACT
Using spectral-luminescent and spectrophotometric methods a composition of aminoacidic (AA) and protein components of commercial drug of heparin (Hep) as well as its interaction with Trp, Tyr and Phe was studied. The impurities of aromatic aminoacids Phe, Tyr and elastin protein was revealed in drug of heparin. The quenching of fluorescence (FL) of Trp, Tyr and Phe with heparin was studied and the Stern-Volmer Constants (K) showing the stability of its complexes with aminoacids were determined. The stability of complexes AA...Hep increases in the series K (Trp...Hep) = 19 +/- 2 M(-1) < K (Tyr...Hep) = 39 +/- 3 M(-1) < K (Phe...Hep) = 710 +/- 70 M(-1), that, probably, determines dominating contribution of Phe impurity in heparin and the absence of that of tryptophan. It was assumed, that animal elastin, which is different from human one can provoke allergic reactions up to anaphylactic shock.
Subject(s)
Heparin/chemistry , Phenylalanine/chemistry , Tryptophan/chemistry , Tyrosine/chemistry , Drug Contamination , Elastin/chemistry , Fluorescence , Heparin/therapeutic use , Humans , SpectrophotometryABSTRACT
Allapinine (lappaconitine hydrobromide) is a drug for the treatment of cardiac arrhythmias, it shows IC class antiarrhythmics properties. Its action mechanism is associated with blockade of Na(+)-channels with subsequent inhibition of the depolarization rate and, consequently, of the slowing and reducing the excitability of the cardiac conduction system. At the moment, it is not established, what factors are associated with side effects of Allapinine, and therefore it seems important to study the molecular mechanisms of its action. The target genes were identified in a rat model of aconitine-induced arrhythmia using a commercial kit "Rat Neuroscience Ion Channels & Transporters RT2 Profiler PCR Array" (SABioscienses). Comparison of the expression of 84 genes in the experimental (aconitine arrhythmias/Allapinine) and control (aconitine arrhythmias/saline) animals revealed changes in the mRNA level of 18 genes. It has been shown an increase in mRNA levels of genes encoding various types of K(+)-channels (kcna6, kcnj1, kcnj4, kcnq2, kcnq4), Ca(2+)-channel (cacna 1g), vesicular acetylcholine transporter (slc 18a3). Decrease in the mRNA level was observed for genes encoding the Na(+)-channel (scn8a), K(+)-channels (kcne 1, kcns 1), membrane transporters (atp4a, slc6a9). Taken together, it appears that the effect of Allapinine on aconitine--induced arrhythmias is due to modulation of genes encoding Na(+)-, K(+)-, Ca(2+)-channels, conducting ionic currents (I(Na), I(to), I(Ks), I(K1), I(CaT)), which are involved in the formation of different phases of the action potential. The effect of the drug on the mRNA levels of genes encoding the acetylcholine and glycine transporters, suggesting the participation of these neurotransmitters in the mechanisms of anti-arrhythmic properties of the Allapinine.
Subject(s)
Aconitine/analogs & derivatives , Anti-Arrhythmia Agents/administration & dosage , Arrhythmias, Cardiac/genetics , RNA, Messenger/genetics , Aconitine/administration & dosage , Aconitine/metabolism , Action Potentials/drug effects , Animals , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/metabolism , Calcium Channels/drug effects , Calcium Channels/metabolism , Gene Expression Regulation/drug effects , Heart Conduction System/drug effects , Male , Potassium Channels/drug effects , Potassium Channels/metabolism , RNA, Messenger/drug effects , Rats , Sodium Channels/drug effects , Sodium Channels/metabolismABSTRACT
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.
Subject(s)
Antiviral Agents/chemical synthesis , Influenza A Virus, H1N1 Subtype/physiology , Papillomaviridae/physiology , Triterpenes/chemical synthesis , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cell Line , Drug Evaluation , Humans , Influenza, Human/diet therapy , Papillomavirus Infections/drug therapy , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
The rare olean-18(19)-ene triterpenoids moradiol and moronic acid were synthesized from betulin, and their antiviral properties were investigated.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Oleanolic Acid/analogs & derivatives , Triterpenes/chemistry , Animals , Antiviral Agents/pharmacology , Cells, Cultured , Chick Embryo , Fibroblasts/cytology , Fibroblasts/virology , Influenza A virus/metabolism , Oleanolic Acid/chemical synthesis , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Triterpenes/pharmacologyABSTRACT
Uraline, a new norditerpenoid alkaloid, was isolated from aerial parts of Delphinium uralense. The structure of 1alpha,7,8-trihydroxy-6beta,14alpha,16beta-trimethoxy-18-N-(2-methyl)succinylanthranoyloxyaconane was ascribed to the new compound on the basis of 1H and 13C NMR, IR, and mass spectra. The known alkaloids methyllycaconitine and delcorine were also isolated from the plant.
Subject(s)
Alkaloids/isolation & purification , Delphinium/chemistry , Diterpenes/isolation & purification , Chromatography, Liquid , Magnetic Resonance Spectroscopy , Mass Spectrometry , Plant Components, Aerial/chemistry , Plant Extracts/chemistryABSTRACT
Experiments on isolated neurons of sensory ganglions of rats aimed to find physiologically active plant drugs were carried out by means of voltage-clamp, intracellular perfusion and "concentration-clamp" methods. Izokorin was shown to exert blocking action on GABA-activated currents as bicuculline and korlumin. It is suggested that other bicuculline-like alkaloids corresponding to isomers can exert the same effect on GABA-activated currents.
