Search

It has been found that natural xanthines, as well as their synthetic analogs, possess the diuretic effect. Analysis of the literature proves that there is a great opportunity of applying synthetic derivatives of N-methylated xanthines as potential diuretics.Aim. To develop preparative methods of the synthesis of 8-aminosubstituted of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine and study their physical, chemical and biological properties. Results. The synthesis of a series of 8-aminosubstituted of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine was carried out. According to the results of the biological testing the compounds synthesized belong to the toxicity of class IV. 7-(2-Hydroxy-3-p-methoxyphenoxypropyl-1)-8-(furyl-2-methylamino)-3-methylxanthine xanthine shows the highest diuretic activity, and hence, requires a more in-depth study since it is twice more active than hydrochlorothiazide. It should be emphasized that all compounds synthesized exhibit a marked diuretic effect. Experimental part. 8-Bromo-7-(2-hydroxy-3-p-methoxyphenoxypropyl-1)-3-methylxanthine was obtained by heating 8-bromo-3-methylxanthine with p-methoxyphenoxymethyloxirane in butanol-1 and in the presence of N,N-dimethylbenzylamine. 8-Aminosubstitutied of 7-(2-hydroxy-3-p-metoxyphenoxypropyl-1)-3-methylxanthine was obtained by boiling of bromoalcohol with the primary and secondary amines. The structure of the compounds synthesized was unambiguously confirmed by NMR-spectroscopy. The acute toxicity of the compounds obtained was studied by Kerber method. The study of the diuretic activity of the compounds was carried out using Ye. Berkhin method. Hydrochlorothiazide was used as a reference substance. Conclusions. Simple methods for the synthesis of 8-amino-7- (2-hydroxy-3-p-methoxyphenoxypropyl-1)-3-methylxanthines have been developed. The structure of the compounds synthesized has been confirmed by the method of NMR 1H-spectroscopy. The acute toxicity and the diuretic activity of the compounds obtained have been studied.

Современные антибиотики и синтетические противомикробные средства занимают лидирующее место в лечении бактериальных инфекций. Несмотря на их эффективность, они вызывают ряд побочных эффектов, следовательно, поиск новых противомикробных и противогрибковых средств – одна из самых актуальных проблем фармацевтической науки. Данные специализированной литературы свидетельствуют, что производные ксантина проявляют активность в отношении некоторых штаммов патогенных микроорганизмов и грибов.Цель работы – разработка метода синтеза новых производных ксантинил-8-аминоалкановых кислот и изучение их физико-химических свойств, противомикробного и противогрибкового действия.Материалы и методы. Температуру плавления определяли открытым капиллярным способом с использованием прибора ПТП-М. Элементный анализ выполнили на приборе Elementar Vario L cube, ПМР-спектры сняты на спектрометре Bruker SF-400 (рабочая частота 400 МГц, растворитель ДМСО, внутренний стандарт – ТМС). Изучение антибактериальной и противогрибковой активности синтезированных веществ проводили по методу двукратных серийных разведений. Для исследования использовались стандартные тест-штаммы: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. В качестве растворителя соединений использовали диметилсульфоксид.Результаты. Реакция 8-бром-7-этилксантинов с избытком соответствующей аминоалкановой кислоты в среде водного ДМФА в присутствии эквимолярного (по отношению к аминокислоте) количества пищевой соды ведет к образованию соответствующих 7-этилксантинил-8-аминоалкановых кислот. Структура синтезированных соединений однозначно доказана методом 1Н ЯМР-спектроскопии. Исследование противомикробного действия синтезированных соединений показало, что тиопроизводные 7-этилксантинил-8-аминоалкановых кислот проявляют умеренную и слабую активность в концентрациях 50–100 мкг/мл.Выводы. Разработана препаративная методика синтеза неописанных в спецаилизированной литературе 7-этилксантинил-8-аминоалкановых кислот. С помощью данных спектроскопии 1Н ЯМР доказано строение синтезированных соединений. Изучено противомикробное и противогрибковое действие полученных соединений. Показана перспективность ксантинил-8-алкановых кислот для дальнейшего поиска биологически активных соединений., Modern antibiotics and synthetic antimicrobial agents play a leading role in the treatment of bacterial infections. Despite their effectiveness, they cause a number of side effects, and thus the search for new antimicrobial and antifungal agents is currently one of the problems of pharmaceutical science of current interest. Literary data suggest that xanthine derivatives exhibit activity in relation to some strains of pathogenic microorganisms and fungi.The aim of this work is to develop a method for the synthesis of new derivatives of xanthine-8-aminoalkanoic acids and to study their physical and chemical properties, as well as their antimicrobial and antifungal effects.Materials and methods. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS). Study of antimicrobial and antifungal activity of synthesized compounds has been performed by a two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds.Results. The reaction of 8-brom-7-ethylxanthines with an excess of the corresponding aminoalkanoic acid in an aqueous DMF medium in the presence of an equimolar (in relation to the amino acid) amount of baking soda leads to the formation of the corresponding 7-ethylxanthinyl-8-aminoalkanoic acids. Structure of synthesized compounds was definitely proved by 1Н NMR-spectroscopy. Conducting primary screening research of antimicrobial activity of 7-ethylxanthinyl-8-aminoalkanoic acids derivatives, which revealed moderate and weak activity in concentrations 50–100 mcg/ml.Conclusions. A preparative method of synthesis of not described in the literature 7-ethylxanthinyl-8-aminoalkanoic acids is developed. The structure of the synthesized compounds has been proved with the help of data of the 1H NMR spectroscopy. The antimicrobial and antifungal effects of the obtained compounds have been studied. The perspective of xanthine-8-alkanoic acids for the further search of biologically active compounds is shown., Сучасні антибіотики та синтетичні протимікробні засоби посідають чільне місце в лікуванні бактеріальних інфекцій. Незважаючи на їхню ефективність, вони викликають низку побічних ефектів, а отже пошук нових протимікробних і протигрибкових засобів нині є однією з найактуальніших проблем фармацевтичної науки. Дані фахової літератури свідчать, що похідні ксантину виявляють активність щодо деяких штамів патогенних мікроорганізмів і грибів.Мета роботи – розробка методу синтезу нових похідних ксантиніл-8-аміноалканових кислот і вивчення їхніх фізико-хімічних властивостей, протимікробної та протигрибкової дії.Матеріали та методи. Температуру плавлення визначали відкритим капілярним способом на приладі ПТП-М. Елементний аналіз виконали на приладі Elementar Vario L cube, ПМР-спектри зняті на спектрометрі Bruker SF-400 (робоча частота 400 МГц, розчинник ДМСО, внутрішній стандарт – ТМС). Вивчення антибактеріальної та протигрибкової активності синтезованих речовин здійснили за методом дворазових серійних розведень. Для дослідження застосували стандартні тест-штами: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Як розчинник сполук використовували диметилсульфоксид.Результати. Реакція 8-бромо-7-етилксантинів із надлишком відповідної аміноалканової кислоти в середовищі водного ДМФА за наявності еквімолярної (щодо амінокислоти) кількості харчової соди призводить до утворення відповідних 7-етилксантиніл-8-аміноалканових кислот. Структура синтезованих сполук однозначно доведена методом 1H ЯМР-спектроскопії. Дослідження протимікробної дії синтезованих сполук показали, що похідні 7-етилксантиніл-8-аміноалканових кислот виявляють помірну та слабку активність у концентраціях 50–100 мкг/мл.Висновки. Розроблена препаративна методика синтезу неописаних у фаховій літературі 7-етилксантиніл-8-аміноалканових кислот. За допомогою даних спектроскопії 1Н ЯМР доведена будова синтезованих сполук. Вивчена протимікробна та протигрибкова дія сполук, що отримали. Показана перспективність ксантиніл-8-алканових кислот для дальшого пошуку біологічно активних сполук.

Широкий спектр биологической активности природных ксантинов стимулировал поиск биологически активных соединений среди их синтетических аналогов, что привело к созданию ряда лекарственных средств (нигексин, сплантин, теокор и др.), которые успешно применяют до настоящего времени. Работа по поиску новых биологически активных соединений среди производных ксантина не останавливается. Установлено, что тиопроизводные ксантина проявляют антиоксидантную, диуретическую, гипогликемическую, противоопухолевую, противомикробную, противовоспалительную, анальгетическую активности.Цель работы – разработка простых препаративных методик синтеза неописанных ранее производных 3-метил-7-этил-ксантина как основы для создания оригинальных лекарственных средств противомикробного и противогрибкового действия.Материалы и методы. Температуру плавления определяли открытым капиллярным способом с использованием прибора ПТП (М). Элементный анализ выполнили на приборе Elementar Vario L cube, ПМР-спектры сняты на спектрометре Bruker SF-400 (рабочая частота – 400 МГц, растворитель – ДМСО, внутренний стандарт – ТМС). Изучение антибактериальной и противогрибковой активности синтезированных веществ проводили по методу двукратных серийных разведений. Для исследования использовали стандартные тест-штаммы: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. В качестве растворителя соединений использовали диметилсульфоксид.Результаты. Кратковременное нагревание 3-метил-7-этил-8-тиоксантина с метилхлорацетатом в водно-спиртовом растворе гидроксида натрия ведет к образованию соответствующего эфира. Гидразинолизом метил(3-метил-7-этилксантинил-8-)тиоацетата получен 3-метил-7-этилксантинил-8-тиоацетгидразид, реакцией которого с ароматическими альдегидами синтезированы соответствующие бензилиденгидразиды 3-метил-7-этил-ксантинил-8-тиоуксусной кислоты. Структура синтезированных соединений однозначно доказана методом ПМР-спектроскопии. Исследование противомикробного действия синтезированных соединений показало, что 8-тиопроизводные 3-метил-7-этил-ксантина проявляют умеренную и слабую активность в концентрациях 50–100 мкг/мл. 2-Метокси-5-бромобензилиденгидразид проявляет выраженное противогрибковое действие.Выводы. Разработана препаративная методика синтеза неописанных в специализированной литературе бензилиденгидразидов 3-метил-7-этил-ксантинил-8-тиоуксусной кислоты. С помощью данных спектроскопии ПМР доказано строение синтезированных соединений и их существование в виде смеси Е- и Z-изомеров в соотношении 2:1. Изучено противомикробное и противогрибковое действие полученных соединений. Установлены приоритеты для дальнейшего поиска биологически активных соединений., A wide range of biological activity of natural xanthines stimulated the search of biologically active compounds among their synthetic analogues, which led to the creation of a number of medicines (Nihexynum, Proxyphyllinum, Protheobrominum, etc.), which have been successfully applied till present time. It should be noted that the search of new biologically active compounds among xanthine derivatives does not stop. Previously, we had found that xanthine thioderivatives exhibits antioxidant, diuretic, hypoglycemic, antitumor, antimicrobial, anti-inflammatory, analgesic activity.The aim of the work is to elaborate simple laboratory methods of 7-ethyl-3-methylxanthine derivatives synthesis, unspecified in scientific papers earlier, – the basis for the creation of original antimicrobial and antifungal medicines.Materials and methods of research. The melting point has been determined with the help of an open capillary method with PTP-M device. Elemental analysis has been performed with the help of the instrument Elementar Vario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO, internal standard – TMS). Study of antimicrobial and antifungal activity of synthesized compounds has been performed by a two-fold serial dilution method. Standard test strains have been used for the study: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Dimethylsulfoxide was used as the solvent of the compounds.Results and their discussion. Under short-time heating up of 7-ethyl-3-methyl-8-thioxanthine with methyl chloroacetate in a water-ethanol solution of sodium hydroxide leads to the formation of the corresponding ester. 3-Methyl-7-ethylxanthinyl-8-thioacethydrazide was obtained by hydrazinolysis of methyl(3-methyl-7-ethylxanthinyl-8-)thioacetate. Corresponding 7-ethyl-3-methylxanthinyl-8-thioacetic acid benzylidene hydrazides were obtained by the reaction of hydrazide with aromatic aldehydes. Structure of synthesized compounds was definitely proved by NMR-spectroscopy. Conducting primary screening research of antimicrobial activity of 8-thioderivatives of 7-ethyl-3-methylxanthine, which revealed moderate and weak activity in concentrations 50–100 mcg/ml. 2-Methoxy-5-bromobenzylidenehydrazide showed a pronounced antifungal effect.Conclusions. The preparative method of synthesis of 7-ethyl-3-methylxanthinyl-8-thioacetic acid benzylidene hydrazides, unspecified in scientific papers earlier, was developed. The structure of the synthesized compounds and their existence in the form of a mixture of E- and Z-isomers in the ratio 2:1 was proved with the help of the NMR spectroscopy data. The antimicrobial and antifungal effects of the obtained compounds were studied. Priorities for further research of biologically active compounds have been outlined., Широкий спектр біологічної активності природних ксантинів стимулював пошук біологічно активних сполук серед їхніх синтетичних аналогів, що призвело до створення ряду лікарських засобів (нігексин, сплантин, теокор тощо), які успішно застосовують донині. Робота з пошуку нових біологічно активних сполук серед похідних ксантину не припиняється. Раніше встановили, що тіопохідні ксантину виявляють антиоксидантну, діуретичну, гіпоглікемічну, протипухлинну, протимікробну, протизапальну, аналгетичну активності.Мета роботи – розробка простих препаративних методик синтезу неописаних раніше похідних 7-етил-3-метилксантину як основи для створення оригінальних лікарських засобів протимікробної та протигрибкової дії.Матеріали та методи. Температуру плавлення визначали відкритим капілярним способом на приладі ПТП (М). Елементний аналіз виконали на приладі Elementar Vario L cube, ПМР-спектри зняті на спектрометрі Bruker SF-400 (робоча частота – 400 МГц, розчинник – ДМСО, внутрішній стандарт – ТМС). Антибактеріальну та протигрибкову активність синтезованих речовин вивчили за методом двократних серійних розведень. Для дослідження застосували стандартні тест-штами: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. Як розчинник сполук використовували диметилсульфоксид.Результати. Нетривале нагрівання 3-метил-7-етил-8-тіоксантину з метилхлорацетатом у водно-спиртовому розчині натрій гідроксиду призводить до утворення відповідного естеру. Гідразинолізом метил(3-метил-7-етилксантиніл-8-)тіоацетату отримали 3-метил-7-етилксантиніл-8-тіоацетгідразид, реакцією якого з ароматичними альдегідами синтезовані відповідні бензиліденгідразиди 7-етил-3-метилксантиніл-8-тіооцтової кислоти. Структура синтезованих сполук однозначно доведена методом ПМР-спектроскопії. Дослідження протимікробної дії синтезованих сполук показали, що 8-тіопохідні 7-етил-3-метилксантину виявляють помірну та слабку активність у концентраціях 50–100 мкг/мл. 2-Метокси-5-бромобензиліденгідразид виявляє виразну протигрибкову дію.Висновки. Розроблена препаративна методика синтезу неописаних у фаховій літературі бензиліденгідразидів 7-етил-3-метилксантиніл-8-тіооцтової кислоти. За допомогою даних спектроскопії ПМР доведена будова синтезованих сполук та їхня наявність у вигляді суміші Е- та Z-ізомерів у співвідношенні 2:1. Вивчена протимікробна, протигрибкова дії цих сполук. Встановлені пріоритети для наступного пошуку біологічно активних сполук.

Despite the wide application of brand-new instruments, continuous improvements in surgical treatment and application of up-to-date antiseptics and disinfectants within the last decade,a risk of infectious complications inhip and knee jointsendoprosthesis replacementstill remains.The most efficient results in post-surgery implant-related infection (IRI) treatment are attained when combining surgical interference with long-term etiotropic therapy, its efficiency being evaluated via balanced selection of antimicrobialagents. “Perfect” antibacterial drug for surgical infection treatment must reveal bactericidal effect against specific infectious agents, form high concentrations in bones, joints and soft tissues and have high safety profile. The challenge is that currently for most part of antibiotics there is no convincing evidence in regards to their application for implant-related infection (IRI). At present it is generally accepted that the leading role of S. Aureus and S. Epidermidis in IRI etiology is largely due to their ability to generate multi-level microbial biofilms quickly at the artificial implants surface. Pathogens’ presence in biofilms makes IRI diagnostics more complicated and significantly reduces the efficiency of antimicrobial therapy. Earlier it has been determined that 1.8-disubstituted of theobromine show rather high diuretic, anti-inflammatory, analgesic, antioxidant, hypolipidemic and antimicrobial activity. Thus, the problem of discovering new highly efficient antimicrobial agents which might be applied in IRI treatment remains relevant and long-termissue. Aim of the work is to develop simple laboratory methods to synthesize 8- benzylidenhydrazino-1-n-propyltheobromines and study biological activity of synthesized compounds. Materials and Methods of Research Themeltingpointhasbeendeterminedwiththehelpofanopencapillary methodwithTAPdevice(M).Elementalanalysishasbeenperformedwiththe help of the instrument ElementarVario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-200 (operating frequency of 200 MHz, solvent DMSO, internal standard – TMS). These data correspond to thecalculated elemental analysis.For the initial screening study of the new synthesized substances there has been usedthebenchmarkscultureasgram-positiveandgram-negativebacteriawhich belongtodifferentmorphologicalpropertiesofclinicallyimportantgroupsof infectiousagents.AsasetofstandardteststrainswehavetakenEscherichiacoli ATSS 25922, Staphylococcus aureus ATSS 25923, Pseudomonas aeruginosa ATSS27853, Candida albicans ATSS 885-653. All test strains have been obtained from thelaboratorycalled"ZaporizhzhyaRegionalLaboratoryCenteroftheState epidemiological station of Ukraine." The sensitivity of microorganisms to promising antimicrobialnewsynthesizedsubstanceshasbeendeterminedaccordingtothe guidelines.Duringthestudiestherehavebeenpreparedtheserialtwo-fold dilutions of the drug in Mueller-Hinton broth in a volume of 1 ml, and then added to each tube 0.1 ml of microbial curtain (106 CFU / ml). We havedeterminedtheminimuminhibitoryconcentration(MIC).Asthe solvent compounds we have used dimethylsulfoxidein the studies, the initial solution hasbeenadjustedtoaconcentrationof1mg/ml.Additionallywehaveheldthe control of culture media and solvent by the conventional methods. Results Heating of 8-bromo-1-n-propyltheobromine with an excess of hydrazine hydrate in aqueous dioxane leads to the formation of 8-hydrazino-1-n-propyltheobromine. Interaction of 8-hydrazinoptheobromine with aldehydes has lead to formation of a range of respective 8-benzylidenhydrazinoderivatives. Structure of synthesized compounds has been definitely proved by NMR-spectroscopy.It has beenfound, that synthesized 8-benzylidenhydrazino-1-n-propyltheobrominesexhibit mild effect.Index of antibacterial activity of some compoundsagainstStaphylococcus aureus and Candida albicans is approaching toAmpicillin andNystatin. Conclusion Suggesting laboratory method to obtain 8-hydrazino-1-n-propyltheobromine, initial synthon for further xanthine molecule modification. Developing accessible laboratory methods to synthesize new 8-benzylidenhydrazino-1-n-propyltheobromines, which are potential bioactive compounds. Studying PMR-spectral characteristics of the obtained substances. Conducting primary screening research of antimicrobial activity of 8- benzylidenhydrazine derivatives, which revealed viability of further search for antistaphylococcal and antifungal drugs within this range.

Diabetes mellitus is a chronic endocrine disease. It etiology is the impact of both endogenous (genetic) and exogenous factors that cause absolute or relative shortage of insulin or not effective use of it, which in turn leads to disruption of all kinds of substances exchange. The study of this problem is actual due to the high prevalence of diabetes, chronic disease, the tendency to increase the number of patients, their high morbidity and mortality. Diabetes is characterized by high blood glucose levels, which eventually leads to various complications associated with many human systems damage. Hormones (insulin and its analogues) and synthetic drugs (sulfonylureas, biguanides etc.) are used For the treatment of diabetes, but their high toxicity, cumulativeness, various side effects (autoimmunization, cutaneous allergic reactions, disturbance of the micro flora of the digestive tract), and the formation of insulin resistance restrict the use of these drugs in clinical practice. On this aspect the attention of researchers is attracted to xanthine derivatives, which are known as substances with wide range of biological activities including hypoglycemic. Based on the above, the search and development of new drugs among new 3-R-substituted xanthine, which would have hypoglycemic effect and would be deprived of most side effects is an acute problem of modern medical and pharmaceutical sciences. The aim of this study was to investigate the hypoglycemic activity of newly synthesized derivatives of 3-benzyl-8-methylxanthine and establish certain patterns "structure-activity" relationship. Materials and methods As objects of study for hypoglycemic activity we used derivatives of 3-benzyl-8-methylxanthine synthesized at the Department of Biochemistry and LaboratoryDiagnostics ofZaporizhzhyaStateMedicalUniversity. Hypoglycemic action of xanthine derivatives evaluated by intraperitoneal glucose tolerance test, which was reproduced by injection to animals (white rats weighing 160-230 g) glucose at a dose of 2 g/kg. The experimental animals were divided in 14 groups of 7 animals in each: 1. Intact – animals administered saline; 2. Control – modeling hyperglycemia without treatment. 3-13. Animals were injected xanthine derivatives at the background of hyperglycemia modeling. 14. The animals were injected metformin at the background of hyperglycemia modeling. We determined glucose level in blood using a glucometer «Accu Chek Active» after 30 and 60 minutes. Research results processed by modern methods of analysis using Student t-test. We used the level of statistical significance of differences of research results - p

Formation of germinal granules during oogenesis was studied in sea cucumbers, Apostichopus japonicus, Selenka, 1867, using transmission electron microscopy. It was found that within the early oogenesis mitochondria interact with a Balbiani body, gradually become immersed into its substance and transformed into electron-dense structures, which are similar to the germinal granules of metazoans. In late oogenesis, formed germinal granules lose their contacts with a Balbiani body and are localized in the cortical portion of the oocyte, near the cell membrane. Vestigial mitochondrial cristae are a typical feature of germinal granules. The obtained data suggest that the process of transformation of mitochondria into germinal granules is one of the functions of the Balbiani body, whose role still remains unexplained.

In this work, we have described the method of 3-benzyl-8-methylxanthinyl-7-acetohydrazide synthesis and studied its reaction with different aldehydes and ketones in acidic medium. As result, we obtained a series of novel ylidenhydrazides of 3-benzyl-8-methylxanthinyl-7-acetic acid. The structure of the synthesized sub­stances was proved by IR and NMR spectra and elemental analysis and their individuality was confirmed by thin-layer chromatography.

Objective: Accumulation of reactive oxygen species and nitric oxide (NO) derivatives in the cell exerts damaging effects on its constituents, such as carbohydrates, proteins, lipids, and nucleic acids. These processes has been determined to play a significant role as a nonspecific pathogenetic mechanism in development of multiple disease states, such as atherosclerosis, ischemic stroke, diabetes, etc. The search for antioxidant compounds capable of interrupting the pathological biochemical processes at various steps of oxidative and nitrosative stress development, and thus exerting prophylactic and therapeutic effects, is a priority for medical and pharmaceutical sciences. In this article we investigated the effects of newly synthesized esters, hydrazides and hydrazones of theophyllinyl-7-acetic acid on late markers of oxidative and nitrosative stresses. Methods: Investigation of antioxidant properties of xanthine derivatives was carried out using following in vitro methods: inhibition of the NO• radical, inhibition of oxidative modification of proteins, and initiation of lipid peroxidation Results: Hydrazides and benzylidene-hydrazides of theophyllinyl-7-acetic acid showed more pronounced antioxidant properties than esters. The most active compounds among tested theophyllinyl-7-acetic acid derivatives were hydrazide and (1-phenylethyliden)hydrazide of (8-N-benzylaminotheophyllinyl-7)acetic acid. Conclusions: In vitro studies of 23 derivatives of theophyllinyl-7-acetic acid have been shown that almost all compounds exhibit antioxidant properties. The obtained results also helped us to establish some patterns of structure-activity relationship.

Background: Acute ischemic stroke is a leading cause of mortality, morbidity, long-term disability in industrialized countries. One of main parts of it pathogenesis is production of reactive oxygen species. The accumulation of them in neurons results in lipid peroxidation, protein oxidation, DNA damage, and finally cell death. Thereby the search of novel drugs, that have antioxidant action and can be used to complex treatment of cerebral strokes is reasonable. It is known, that xanthine derivatives exhibit a broad spectrum of biological activity, including antioxidant. So that, the goal of this research was to study in vivo neuroprotective action of water-soluble derivative of 3-benzylxanthine – morpholin-4-ium 3-benzylxanthinyl-8-methylthioacetate (Ale-15 compound) in comparison with neuroprotector-antioxidant – Mexidol. Methods: Experimental part was done on white Wistar rats of both sexes of 220-260 g weight. For assessment of neuroprotective action of compound we used a model of global incomplete cerebral ischemia, that was reproduced by bilateral common carotid arteries ligation. Results: It was studied an acute toxicity of Ale-15 compound, it influence on survival of laboratory animals, on progression of neuralgic deficit, on the content of adenylic nucleotides, on criteria of energy metabolism, on the activity of antioxidant enzymes and on oxidative modification of protein. Results of study showed, that injection of Ale-15 compound to animals with ischemic stroke intragastrically during 4 days positively reduced death rate and quantity of animals with serious neurologic symptoms. The main parts of Ale-15 cerebroprotective mechanism are antioxidant and anti-ischemic actions. Conclusions: The performed study revealed significant cerebroprotective features of Ale-15 compound in conditions of experimental cerebrovascular accident.

For cultivation of Aedes togoi the aquatic infusion of fallen leaves, peat and dry sphagnum (0.15%S) was used and a larval diet (children's haematogen with an addition of polyvitamin "Undevit" and glutamic acid) was offered. Such cultural medium provides a rapid development of larvae and their survival, high stable weight of pupae, high fecundity and viability of imago. 7 generations were obtained without reducing the quality of culture.

The biology of Aedes impiger Walk. from the polar region of the European part of the USSR has been studied and literary data have been summarized. Its biological peculiarities such as rapid and simultaneous development of larvae and pupae, a short period of seasonal activity, long daily activity, the presence of autogeny and long obligate diapause provide a distinct localization of the active period of the life cycle within a season. A. impiger develops quicker than other spring species of mosquitoes, emerges the first and can serve as phenoindicator for specification of developmental periods and mass emergence of bloodsucking mosquitoes.