Coordination compounds of essential microelement germanium(IV) with metals (Mg, Na, K, Ca, Cu, etc.) and organic ligands -biocatalysts, antidotes at intoxications and regulators of mineral metabolism in living organism (nicotinic, citric, tartaric, 1-hydroxyethylidendiphosphonic acids, nicotinamide) are synthesized for the first time on the Department of General Chemistry and Polymers of Odessa Mechnikov National University. The favorable activity of the synthesized compounds on cardiovascular and chronic respiratory diseases, senile pneu-on cardiovascular and chronic respiratory diseases, senile pneumonia, neuropsychiatric and metabolic disorders, ischemic heart diseases, etc. is described. Thus, the influence of 1-hydroxyethylidendiphosphonatogermanate (medgerm) on CNS, its anxiolytic activity and absence of both hypnotic and myorelaxant effects has been shown. Cardioprotector properties of magnesium hydroxyethylidendiphosphonategermanate as a potential effective and safe drug with the high antihypertensive and antiarrhythmic activity have been found out. The interferoninductive and immunostimulatory activity of germanium(IV) compounds with 1-hydroxyethylidendiphosphonic, nicotinic acids, nicotinamide, pyracetam has been studied. Injection of these drugs (concentration 100-125 μg/ml) causes the 100 % delay of cytopathic action of vesicular stomatitis virus in the cell cultures that demonstrates the ability of compounds to increase essentially cells stability. The perspectives of germanium coordination compounds as interferon inductors and as immune pharmaceuticals for prevention the disbalance of the immune system are reviewed.
Background. Stroke is among the leading causes of death and disability worldwide with rising incidence among young people today. This is the third most common cause of disability-adjusted life-years worldwideObjective. The present study evaluated the cerebroprotective action of coordination compounds of germanium with underlying global cerebral ischemia in rats.Methods. Global cerebral infarction was induced by bilateral common carotid artery occlusion. For primary screening we used numerous bis(citrate) germanates (stannates) compounds, which contained different metals: OL1-8, and VITAGERM-1,2,3 and 4. All germanium complexes used were injected intraperitoneally (1 % aqueous solution at a dose of 50 and 100 mg/kg in 35 min after bilateral common carotid artery occlusion). Piracetam was used as a reference drug. Criteria of cerebroprotection efficacy: survival of rats (%), ET50 (median effective time), observational Irwin’s test.Results. Almost all bis(citrate) germanates (stannates), which contained different metals, possessed anti-ischemic activity of different intensity. The exceptions were cobalt-containing OL-6 and OL-2 compounds. The most significant efficacy of all investigated indices (which exceeded even reference drug) was evidenced for VITAGERM-1 – a coordination compound of germanium, diethylenetriaminepentaacetic acid and lithium. Conclusions. Results of our experiments are the substitution for further more profound pharmacological investigation of VITAGERM-1 for stroke cerebroprotection and its implementation into clinics.
Background. Previous studies showed that new coordinate compound Cerebrogerm (ferrum bis(citrato)germanate) is a promising cerebroprotector. Objective of the study is a comparative analysis of the central stage of the pharmacokinetics of Cerebrogerm as well as its distribution in vital organs in cases of closed head injury. Methods. On the experimental original model of closed brain injury in rats the parameters of the central stage of Cerebrogerm pharmacokinetics: the distribution in brain, liver, kidneys, were studied. Results. It is established that, in cases of closed head injury Cerebrogerm reaches maximum concentration first in the brain (in 3.75 h), then in the kidneys (in 3.92 h), and finally in the liver (in 4.17 h). In this case, the magnitude of the Cmax of the coordinating compound of germanium that is being investigated in different biosubstrates of the rats with closed head injury may be presented in descending order as follows: brain (7.95 mg/L) > liver (6.22 mg/L) > kidneys (1.79 mg/L). Conclusions. The compound Cerebrogerm studied easily gets through the blood-brain barrier and meets the present requirements for cerebroprotectors and antihypoxants. The attained results allow noting that in the early post-traumatic period of closed head injury, the blood circulation in the kidneys does not change and cannot modify the absorption-elimination processes of xenobiotics. It has been also established that Cerebrogerm is distributed faster in the examined organs in cases of closed head injury. The highest concentration of the drug is present in the brain and the smallest one – in the kidneys.
The possibility of using a number of bimetallic complexes of germanium (IV) - zinc / cobalt (II) / nickel (II) / cuprum (II) with hydroxycarboxylic acids as modifiers of unsaturated oligoester in the processes of its copolymerization with methyl methacrylate has been investigated. The modification was carried out by adding the corresponding complex to the reaction mixture during the polycondensation of maleic and phthalic anhydride with ethylene glycol at 175 °C. The kinetics of copolymerization at the initial stages was studied by dilatometry at temperatures from 50 °C to 60 °C. It has been shown that the modified polyglycolmalenatephthalate with the studied complexes can significantly increase the rate and reduce the temperature coefficient of the reaction during its copolymerization with methyl methacrylate. The advantages of the studied coordination compounds as modifiers in comparison with unmodified systems and 1,10-phenanthroline have been proved. The effect of the modifier (1,10-phenanthroline), depending on its content in the modified polyglycolmalenatephthalate, on the kinetic characteristics of copolymerization with methylmethacrylate in the range from 0 to 0.5 mol/L was investigated. The calculations of the influence of the temperature coefficient of reaction on the maximum allowable diameter on the example of a spherical sample when reaching a critical temperature of 90 0C for non-isotremic copolymerization processes. Physico-mechanical characteristics have been studied and it has been shown that the addition of a modifier does not significantly change them. In addition, germanium (IV) compounds retain a higher oxidation state, which makes it possible to use the finished polymer product as a biological material for special purposes. The proposed methods can be used to improve the characteristics of semi-finished products in the industrial production of copolymer products without significant changes in the technological process.
Objective. To study the antimicrobial activity of double coordination compounds with 1,10-phenanthroline/2,2ʹ-bipyridine complexes of Fe(II)/Co(II)/Ni(II)/Cu(II) as cations and diff erent tartratogermanate(IV) anions, reveal the main factors of their effi ciency and establish relations between their composition, structure features, and biological properties. Methods. The developed synthesis method allowed us to obtain three diff erent tartratogermanate anions, which exist together in the solution and can be selectively recognized by the certain type of 1,10-phenanthroline/2,2ʹ-bipyridine cation. Th e antimicrobial activity of the compound was investigated by a rapid twofold dilution method in a standard liquid nutrient medium (Hottinger digestion) to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). Results. Th e complex nature of studied compounds, synergism of their biologically active structural units, and the presence of diff erent types of intermolecular bonds result in the high antimicrobial activity against a wide range of microorganisms such as gram-positive Planococcus citreus, Microcoсcus luteus, Bacillus cereus, Staphylococcus aureus, Streptococcus lactis, and, in a less degree, gram-negative Escherichia coli and Agrobacterium tumefaciens. Compounds (1)—(8) show a high antimicrobial activity because all of them belong to the type of double coordination compounds and contain similar structural units. Nevertheless, complexes (1) (23.44 μg/mL), (3) (46.9 μg/mL), (4) (23.44 μg/mL), and (8) (46.9 μg/mL) turned out to be the most eff ective, while (6) (>500 μg/mL) and (7) (>500 μg/mL) are less productive. Complexes that have anions [Ge2(OH)(H2Tart)(μ-Tart)2]3- (1), (8) and [Ge2(OH)(HTart)(μ-Tart)2]4- (4) with free hydroxyl and carboxyl groups of the terminal tartaric acid are able to interact with metals in the enzymes of microorganisms and appear to be better antimicrobial drugs because they show lower inhibitory and bactericidal concentrations. Conclusions. Structural features such as the cation-anionic type of compounds, variability of intermolecular interactions, joint of diff erent biologically active units and free chelating groups in tartaric ligands lead to the combination of different action mechanisms and exclude the possibility of strain resistance.
Відомо, що гіперініціація вільнорадикального окислення фосфоліпідів мембран церебральних нейронів у місці первинного ушкодження за умов закритої черепно-мозкової травми відіграє ключову роль у патогенезі цього екстремального стану. Отже, для переривання даного ланцюгового механізму вторинного пошкодження мембран нейронів принципове значення має здатність потенційних церебропротекторних засобів реалізовувати антирадикальний захист головного мозку, що буде визначати характер перебігу та наслідки закритої черепно-мозкової травми.Раніше проведеними нами скринінговими дослідженнями на моделі закритої черепно-мозкової травми встановлена висока лікувальна ефективність вперше синтезованої координаційної сполуки ферум біс(цитрато)германат (цереброгерм).Метою дослідження було провести в динаміці біохемілюмінесцентний аналіз фармакотерапевтичної дії цереброгерму за умов закритої черепно-мозкової травми.Експериментально доведено, що досліджувана оригінальна координаційна сполука реалізує високу антирадикальну активність, на що вказує модифікація всіх параметрів біохемілюмінесцентного світіння на моделі закритої черепно-мозкової травми. Більше того, цереброгерм здатен ефективно сприяти збереженню пула ендогенних антиоксидантів, за рахунок чого частота обривів вільнорадикальних ланцюгових реакцій переважає над частотою його розгалужень і, як результат, процес ліпідного переокиснення, ініційований за умов травматичного пошкодження головного мозку, піддається різкому гальмуванню.
Мета дослідження – провести комплексний порівняльний фармако-математичний аналіз ефективності координаційних сполук германію з біолігандами у посткомпресійному періоді на підставі результатів скринінгу потенційних засобів фармакотерапії наслідків синдрому тривалого розчавлювання (СТР). Експериментальною моделлю ендотоксикозу посттравматичного генезу був патологічний процес, який розвивався у тварин у результаті розчавлювання м’яких тканин задніх кінцівок протягом 5 год у спеціальному приладі з манометричним контролем тиску. Кількісними критеріями фармакотерапевтичної ефективності досліджуваних сполук в умовах ендотоксикозу на тлі СТР були концентрація кінцевих продуктів перекисного окиснення ліпідів (ПОЛ), що реагують з 2-тіобарбітуровою кислотою (ТБК-реактанти) у гомогенаті печінки щурів і рівень молекул середньої маси (МСМ) у сироватці крові щурів. Кореляційні залежності «структура – активність» проводили за методом найменших квадратів. За результатами скринінгової серії досліджень потенційних засобів фармакотерапії наслідків СТР проведений комплексний фармако-математичний аналіз активності координаційних сполук германію з біолігандами. Показано, що ефективна детоксикація організму за умов СТР притаманна сполукам германію з комплексним органічним аніоном – (Мігу-4-6,8,9). Максимальну здатність зменшувати вміст універсальних маркерів ендогенної інтоксикації проявила сполука (Мігу-6), у разі введення якої рівень МСМ знижується в 2 рази, а концентрація ТБК-реактантів знижується в 4,4 разу порівняно з контрольною групою. Показано, що між концентрацією ТБК-реактантів у гомогенаті печінки щурів і вмістом МСМ у сироватці крові щурів існує залежність, коефіцієнти кореляції (детермінації) якої змінюються в незначному ступені за порівняння різних груп без тіотриазоліну та таких, що містять і тіотриазолін, зокрема, коефіцієнт лінійної кореляції для групи А та групи А1 становить 0,986 і 0,908 відповідно. Отримані дані вказують на правильність вибору тіотриазоліну як препарату порівняння за умов екстремального стану, що вивчається, та можуть бути фармако-математичним обґрунтуванням доцільності його використання на етапі клінічних досліджень. Залежність показників МСМ і ТБК-реактантів від кількості акцепторів та донорів водневого зв'язку, дипольного моменту, енергій ван-дер-ваальсових та електростатичних взаємодій характеризується показниками – коефіцієнтами кореляції та детермінації (rxy, R2) різного рівня. Для показника МСМ найхарактернішим є зв'язок з акцепторами водневого зв'язку (rxy = 0,931, група С), тоді як для показника ТБК-реактантів зв'язок з акцепторами водневого зв'язку характеризується значенням rxy на рівні 0,481 (група С).
α-L-Rhamnosidase [EC 3.2.1.40], enzyme of the hydrolase family has a wide range of applications: in the food industry, for example, in winemaking to improve the quality and aroma of wines, in the production of citrus juices and drinks to remove bitter components (naringin) that improves the quality and nutritional value of these products; in research as an analytical tool for studying the structure of complex carbohydrate-substituted biopolymers. For the successful use of α-L-rhamnosidases in various biotechnological processes, an important aspect is the development of ways to increase their activity. The main factors affecting the growth and metabolism of microorganisms, including the synthesis of enzymes, are the physicochemical conditions of cultivation, the composition of the nutrient medium, the introduction of substances that raise the yield of the enzyme, which is manifested in an increase in its activity. At present, one of the priority directions of modern research is the study of the effect of various effector compounds that are capable to modify the studied enzymatic activity. In this work, which is a continuation of previous studies, a number of mixed-ligand and mixed-ligand-different-metal coordination germanium compounds of with xylaric acid (H5Xylar), 1,10-phenanthroline (Phen), 2,2-bipyridine (bipy) and ions of 3d-metals (Fe2+, Ni2+, Cu2+, Zn2+) were selected as effectors. Study of the effect of these complexes on the activity of Eupenicillium erubescens, Cryptococcus аlbidus and Penicillium tardum α-L-rhamnosidases were the aim of this work. Methods. The objects of research were α-Lrhamnosidases from Eupenicillium erubescens 248, Cryptococcus albidus 1001, and Penicillium tardum IMV F-100074. The α-L-rhamnosidase activity was determined by the Davis method using naringin as a substrate. We used 12 coordination compounds of germanium as modifiers of enzyme activity, the composition and structure of which were established using a combination of physical and chemical research methods: elemental analysis, thermogravimetry, IR spectroscopy and X-ray structural analysis. Structures of seven compounds are deposited in the Cambridge Crystallographic Database. When studying the effect of various compounds on the activity of enzymes, concentrations of 0.1 and 0.01% were used, exposure times were 0.5 and 24 hours. The test compounds were dissolved in 0.1% dimethyl sulfoxide. UV-spectra of absorption of native and chemical modified preparations of the enzymes were studied by spectrophotometer-fluorimeter DeNovix DS-11 in the range of 220–340 nm, concentration of the enzyme preparation 1.0 mg of protein/mL. Results. Analysis of the totality of the obtained data (exposure time 24 h, concentration 0.1%) regarding the effect of the studied compounds on the activity of E. erubescens, C. albidus and P. tardum α-L-rhamnosidases showed that the influence of the studied modifiers for the activity of α-L-rhamnosidases varies depending on the producer strain. Our data allow us to present the following series of modifiers in accordance with an increase in their effect on the activity of enzymes of different producers: E. еrubescens: 12 < 11 < 5 < 3 < 4=10 < 1 < 3 < 8 < 2 < 6 < 7; C. albidus: 10 < 11 < 12 < 9 < 3 < 1=5 < 8=4 < 2 < 6 < 7; P. tardum: 12=2 < 3 < 4 < 11 < 5 < 8 < 1 < 9 < 6 < 10 < 7. Conclusions. The results obtained allow us to conclude that compound (7)(-tris(bipyridine) nickel(II) μ-dihydroxyxylaratogermanate(IV)) is the most effective activator of α-L-rhamnosidases of all three micromycete strains, compound (6)(tris(phenanthroline)nickel(II) μ-dihydroxyxylaratogermanate(IV)) − on α-L-rhamnosidase from E. erubescens and C. albidus, while compound (10)-(copper(II) μ-dihydroxyxylaratogermanate(IV)-cuprate(II)) − only of P. tardum α-L-rhamnosidase.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.