We studied the stability of plasma samples spiked with sulfur mustard (SM) and urine samples spiked with the SM metabolite, 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE), upon long-term storage. The stability of biomarkers in biomedical samples was evaluated by measuring the concentrations of spiking chemicals during the storage at 4 and 30°C. Plasma samples were analyzed by GC–MS/MS for SM regenerated from protein adducts under the action of conc. HCl and by HPLC–HR-MS/MS for albumin adduct [S-HETE]-CPF. Urine was analyzed for intact SBMSE by HPLC–HR-MS/MS, and SBMSE reduced to 1,1'-sulfonylbis[2-(methylthio)ethane] was determined after its conversion with TiCl3 followed by GC–MS/MS measurements. A reference compound of SBMSE was synthesized and characterized in terms of authenticity and quantitative content. Procedures for the quantification of SM markers in biomedical samples in the concentration range 1–100 ng mL–1 were validated. The plasma samples were stable upon storage at 4 and 30°С for at least 41 days after spiking, whereas the urine samples proved to be unstable upon long-term storage at elevated temperatures. The results of the present study can be taken into account in selecting conditions for the transportation and storage of biosamples and for interpreting the results of the determination of the SM biomarker in samples from individuals affected in incidents related to exposure to sulfur mustard.

Introduction. The development of improved formulations of antidotes and remedies, which can be used not only by qualified medical personnel, but also in self- and mutual assistance, is an urgent task for extreme medicine.Objective. Evaluation of the possibility of using nanoscale polymer delivery systems for medicines and antidotes intended for intranasal administration (into the nasal cavity) in extreme medicine.Discussion. The main submicron-sized polymer carriers which are promising as the basis for the creation of an intranasal form of antidotes are identified. The bioavailability of the substance delivered is dependent on the physico-chemical properties of the carrier, the conditions for its production, as well as physiological and anatomical factors. Data is presented regarding possible ways of correcting these factors in order to increase bioavailability. Examples of the use of polymer nanocarriers in the treatment of poisoning with heavy metals and rocket fuel components, as well as lesions caused by radioactive substances, are presented. It is shown that carriers (dendrimers, cyclodextrins) can act as antidotes in certain cases. The study presents a list of antidotes approved for use within the territory of the Russian Federation, for which the development of intranasal forms is possible, taking their physico-chemical and pharmacokinetic properties into account.Conclusions. Following a review of literature sources, the most promising submicron-sized polymer carriers for the intensification of intranasal delivery of drugs and antidotes are herein proposed: dendrimers, liposomes, nanocapsules, nanoparticles, and cyclodextrins. Using the list of antidotes approved for use in the Russian Federation as an example, promising drugs that can be potentially developed on the basis of these carriers are proposed.

Development of drug delivery systems based on branched biocompatible polymers is one of the most promising areas of modern nanopharmaceutics. Researchers have been exploring this area several decades now, and the results of their efforts quickly find their way into production. Dendrimers, a new class of universal synthetic polymers with a highly functional surface, have a number of unique properties: constant size, high degree of branching, multivalence, solubility in water, definite molecular weight, internal cavities. With the release of VivaSol gel, the first dendrimer-based commercialized product, the "model range" of dendrimer carriers has grown significantly. Poly(amide-amine) (PAMAM) dendrimers, which consist of an alkyldiamine core and tertiary amine branches, are believed to be among the most promising compounds that can be used in the development of the new generation drugs. However, they were kept out of the list of clinically acceptable compounds for a long time because of their toxicity, unclear behavior in living systems and pharmacokinetic profile, as well the difficulties associated with establishing a therapeutic dose. This review presents basic information about PAMAM dendrimers and attempts to assess the prospects of their application in treatment of various diseases, including COVID-19.

Показатель липофильности (logP) можно определять ВЭЖХ-методом в соответствии с принципами, отраженными в руководстве ОЭСР: «Partition Coefficient (n-Octanol/Water), High Performance Liquid Chromatography (HPLC) Method» (1989г.).Целью исследования являлось изучение влияния состава подвижной фазы и влияния типа модифицированного сорбента хроматографической колонки (С8/С18) на качество оценки липофильности ряда известных фармакологических средств ВЭЖХ-методом.Для построения калибровочной зависимости нами были предложены веществаионизирующиеся лекарственные средства, с хорошо изученной лиофильностью.В зависимости от комбинации подвижной фазы и хроматографической колонки получили 4 калибровочных зависимостей зависимости logP от логарифма коэффициента удерживания стандартных образцов (logk).По полученным калибровочным зависимостям рассчитали коэффициенты распределения для модельных веществ.

The global opioid crisis requires a paradigm shift in medical use of opioids, the development of methodology to reduce illicit drug use, and development of drug addiction treatment and antidotes. USA target program - HEAL Initiative is implemented under the scientific guidance of NIH with active participation of FDA, CDC and military medicine institutions. The situation in Russian Federation is characterized by a combination of high illegal consumption of dangerous opioids with an extreme shortage of potent analgesics, drugs for treatment addiction and overdose and rudimentary choice of drug formulations. There isn’t any development of innovative substances and preparations of strong analgesics and antidotes, but also a competent analysis of the subject area and vision of directions for the development. The data analysis shows need to replace some of traditionally used mostly natural and semi-synthetic narcotic analgesics (with low therapeutic index, unsatisfactory pharmacokinetics and severe side effects) to promising synthetic opioids and non-narcotic analgesics. Use of prodrugs, synergistic combinations, conjugates and co-drugs is justified. Prospective dosage forms of compounds and pharmaceutical preparations for development of wide range of improved therapeutics should combine: high analgesicactivity, high therapeutic index, minimum values of Tmax and t1/2ke0, positive values of LogBB, distribution coefficient logD7,4 in the interval from 1 to 3. This combination of key properties is necessary for effectiveness and safety of CNS-specific drugs and also allows development on their basis wide range of dosage forms (injectable and non-injectable drugs, fast-acting and prolonged drugs). First of all it is desirable to replace some obsolete injecting and oral preparations (especially with fast and uncontrolled release) to fast-acting transmucosal formulations with targeted pharmacokinetic properties. In order to analyze best practices, develop a strategy for highly effective controlled medicinal and veterinary drugs (analgesics, anesthetics, antidotes and other vital therapies) and coordinate theirdevelopment and production it is necessary to create competent management structure combining the tasks of provision of civilian population and personnel of national defense agencies of effective and safe drugs.

The global opioid crisis requires a paradigm shift in medical use of opioids, the development of methodology to reduce illicit drug use, and development of drug addiction treatment and antidotes. USA target program - HEAL Initiative is implemented under the scientific guidance of NIH with active participation of FDA, CDC and military medicine institutions. The situation in Russian Federation is characterized by a combination of high illegal consumption of dangerous opioids with an extreme shortage of potent analgesics, drugs for treatment addiction and overdose and rudimentary choice of drug formulations. There isn’t any development of innovative substances and preparations of strong analgesics and antidotes, but also a competent analysis of the subject area and vision of directions for the development. The data analysis shows need to replace some of traditionally used mostly natural and semi-synthetic narcotic analgesics (with low therapeutic index, unsatisfactory pharmacokinetics and severe side effects) to promising synthetic opioids and non-narcotic analgesics. Use of prodrugs, synergistic combinations, conjugates and co-drugs is justified. Prospective dosage forms of compounds and pharmaceutical preparations for development of wide range of improved therapeutics should combine: high analgesicactivity, high therapeutic index, minimum values of T max and t 1/2 k e 0 , positive values of LogBB, distribution coefficient logD 7,4 in the interval from 1 to 3. This combination of key properties is necessary for effectiveness and safety of CNS-specific drugs and also allows development on their basis wide range of dosage forms (injectable and non-injectable drugs, fast-acting and prolonged drugs). First of all it is desirable to replace some obsolete injecting and oral preparations (especially with fast and uncontrolled release) to fast-acting transmucosal formulations with targeted pharmacokinetic properties. In order to analyze best practices, develop a strategy for highly effective controlled medicinal and veterinary drugs (analgesics, anesthetics, antidotes and other vital therapies) and coordinate theirdevelopment and production it is necessary to create competent management structure combining the tasks of provision of civilian population and personnel of national defense agencies of effective and safe drugs.

The title compound was synthesized as an internal standard for the quantitative determination of Arimistane in biological samples. [2H7] Arimistane was obtained from Arimistane-d0 by alkaline H/2H exchange of the С2,4,6,8,16 protons. The location of the labels was confirmed by NMR spectroscopy. The spatial structures were studied by X-ray diffraction.

Aminomethylation of guanidine hydrochloride with aqueous formaldehyde and simplest amino acids depending on the reagents ratio results in bicyclic hydrochlorides (1: 4: 2) or tricyclic iminium chlorides (1: 6: 3) that in their turn may be converted into internal salts: zwitter-ions or betaines respectively.

The research persue an understanding of the effects dimetpramide succinate (DMPs) new salt form of dimetpramide (an antiemetic drug) has on the function of the isolated rat heart. We have assessed the dose/concentration -effect correlation. It was proven, that in 1x10-4 M concentration, which corresponds with the dosage recommended for the oral administration, DMPs has strong negative chronotropic and dromotropic effect, along with a moderate vasoconstrictor effect. The mechanism of action DMPs has on an isolated heart differs from the central mode of action, only partially causes the dopamine receptors block. The effect DMPs has on the cardiac muscle carried out via the voltage gated K+-channels.

A new 19-oxa-tricyclohenicosatetraenone and a new dioxacyclopropacycloundecene-10-carboaldehyde and its 6,7-dihydro derivative, named saponaroxins A-C, were isolated from the culture filtrate of Alternaria saponariae a fungal pathogen of the well-known medicinal plant Saponaria officinalis. Saponaroxins A-C were characterized by spectroscopic methods. When assayed on punctured leaf segments of two weeds, Sonchus arvensis and Elytrigia repens saponaroxins B-C were found to be phytotoxic. They demonstrated moderate antimicrobial activity and low toxicity against Paramecium caudatum. Saponaroxin A was acutely toxic to P. caudatum while showed no phytotoxic nor antimicrobial activity. (C) 2016 Elsevier Ltd. All rights reserved.

The anthropogenic pollution along the coastline of the eastern Gulf of Finland was studied through a range of methods, including analyses of metal contamination in water, surface sediments, accumulated algal biomass and its correlation with resistant microbiota. According to concentrations, the main pollutants in water were copper and manganese. Influence of Nuclear Power Plant was remarkable in adjacent areas and was expressed in high concentrations of molybdenum, nickel, copper and other elements in the water. Relatively high concentrations of copper, lead and zinc were found in sediments. Microbial tolerance appeared to be correlated with the concentration of the metals in sediments. Higher tolerance levels were found in sediment samples from more polluted stations. Macroalgae, which were massively developed in the coastal zone, had shown high level of metal bioaccumulation. Analyses of carbon, nitrogen and phosphorus content of algal tissues allowed the estimation of additional nutrient loading from accumulated decaying algal biomass on the coastal zone of the eastern Gulf of Finland. Mass development of algae in coastal area may contribute to accumulation of organic matter and associated metals. In our study the highest metal concentrations in sediments were found at the sites with dense and continuous layer of fresh and decaying macroalgal biomass, accompanied by hypoxic conditions. Also our study has shown that accumulated biomass may be a significant source of nutrients in the coastal ecosystem.

Chloromonilicin was isolated for the first time from Alternaria sonchi , a mycoherbicide proposed for the control of the noxious weed Sonchus arvensis . The already known alternethanoxins A and B and the three recently isolated phytotoxic polycyclic ethanones named alternethanoxins C–E were also isolated from the same source. Chloromonilicin was identified by spectroscopic data (essentially one-dimensional NMR, 2-dimensional NMR and high-resolution ESI-MS) and its structure was confirmed by single X-ray analysis, which also allowed the assignment of the absolute configuration. This latter was independently confirmed by electronic CD calculations. When chloromonilicin was tested for its antimicrobial activity, it was active at concentrations 0.5–1 μg per disc against four bacterial species and a yeast fungus. The compound inhibited conidial germination of four plant pathogens at concentration of 1–10 μg ml −1 . No phytotoxic activity of this antibiotic by leaf-disc puncture bioassay was detected.

Three new polycyclic ethanones, named alternethanoxins C-E, were isolated together with the well-known and closely related alternethanoxins A and B, from the solid culture of Alternaria sonchi, a fungal pathogen proposed for perennial sowthistle (Sonchus arvensis L.) biocontrol. Alternethanoxins C-E were characterized by spectroscopic methods (essentially NMR and HRESI MS) as 2'-dihydroxymethyl-2,5,6,6'-tetrahydroxy-3'-methoxy-biphenyl-3-carboxylic acid methyl ester, 1,4,6,9,10-pentahydroxy-7-methoxy-6H-benzo[c]chromene-2-carboxylic acid methyl ester, and 7,9-dihydroxy-2-methoxy-9H-4,8-dioxa-cyclopenta[def]phenanthrene-5-carboxylic acid methyl ester. When assayed on leaf segments of weeds (Sonchus arvensis and Elytrigia repens), alternethanoxins A and C showed phytotoxic activity inducing notable necrotic lesions. Alternethanoxins C and D possess notable antimicrobial activity when tested against Bacillus subtilis (MIC 10 μg/disc) and Candida tropicalis (MIC 25 μg/disc). Alternethanoxins A and B had low activity against these microbes, while alternethanoxin E was inactive.

ChemInformVolume 46, Issue 16 Heterocyclic Compounds ChemInform Abstract: Unexpected Formation of a Tricycle (I) in the Reaction of 1,3-Bis(hydroxymethyl)urea with Propane-1,3-diamine. Fares Hamoud, Fares Hamoud St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorS. M. Ramsh, S. M. Ramsh St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorL. M. Pevzner, L. M. Pevzner St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. S. Fundamensky, V. S. Fundamensky St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. V. Gurzhiy, V. V. Gurzhiy St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. I. Zakharov, V. I. Zakharov St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. A. Kuznetsov, V. A. Kuznetsov St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorD. V. Krivorotov, D. V. Krivorotov St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorE. S. Khrabrova, E. S. Khrabrova St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this author Fares Hamoud, Fares Hamoud St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorS. M. Ramsh, S. M. Ramsh St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorL. M. Pevzner, L. M. Pevzner St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. S. Fundamensky, V. S. Fundamensky St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. V. Gurzhiy, V. V. Gurzhiy St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. I. Zakharov, V. I. Zakharov St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorV. A. Kuznetsov, V. A. Kuznetsov St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorD. V. Krivorotov, D. V. Krivorotov St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this authorE. S. Khrabrova, E. S. Khrabrova St. Petersburg State Inst. Technol., St. Petersburg 190013, RussiaSearch for more papers by this author First published: 02 April 2015 https://doi.org/10.1002/chin.201516270Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue16April, 2015 RelatedInformation

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

papaverine and its derivatives react with p-chlorophenacyl bromide to give the corresponding quaternary salts, which are converted into pyrrolo[2,1-a]isoquinolines by the action of bases.