Facile cross-link method to synthesize chitosan-based adsorbent with superior selectivity toward gold ions: Batch and column studies.

The recovery of gold from wastewater has received significant attention in the last years due to its high economic value and low availability. A novel chitosan-based adsorbent (CS-GTU) was successfully synthesized by using formaldehyde as a crosslinker between chitosan and guanylthiourea, and applied for selective adsorption of AuIII from an aqueous medium. Through batch experiments, the maximum adsorption capacity of CS-GTU for AuIII could reach up to 695.63 mg/g at pH 5.0, and the adsorption process followed the Pseudo-second-order kinetic and Langmuir isotherm models, indicating that the monolayer chemisorption possibly occurred on the adsorbent surfaces. The adsorption was an enthalpy driven and spontaneous chemical process based on thermodynamic analysis. Furthermore, the adsorbent has demonstrated outstanding selectivity toward AuIII from multi-metallic solutions, and five cycled experiments of adsorption-desorption showed that CS-GTU could be efficiently regenerated. Experimental breakthrough curves were successfully simulated by using the Thomas model, which can fit the experimental data with the correlated curve (R2 > 0.9) well. This improvement in adsorption was a consequence of the complexation and electrostatic attraction of gold ions with the abundant sulfur/nitrogen-containing groups. The CS-GTU beads can be considered as a suitable and efficient adsorbent for gold ions in aqueous solutions.

Design, synthesis and biological evaluation of 4-aminoquinoline-guanylthiourea derivatives as antimalarial agents.

Guanylthiourea (GTU) has been identified as an important antifolate antimalarial pharmacophore unit, whereas, 4-amino quinolones are already known for antimalarial activity. In the present work molecules carrying 4-aminoquinoline and GTU moiety have been designed using molecular docking analysis with PfDHFR enzyme and heme unit. The docking results indicated that the necessary interactions (Asp54 and Ile14) and docking score (-9.63 to -7.36 kcal/mmol) were comparable to WR99210 (-9.89 kcal/mol). From these results nine molecules were selected for synthesis. In vitro analysis of these synthesized compounds reveal that out of the nine molecules, eight show antimalarial activity in the range of 0.61-7.55 µM for PfD6 strain and 0.43-8.04 µM for PfW2 strain. Further, molecular dynamics simulations were performed on the most active molecule to establish comparative binding interactions of these compounds and reference ligand with Plasmodium falciparum dihydrofolate reductase (PfDHFR).

Guanylthiourea derivatives as potential antimalarial agents: Synthesis, in vivo and molecular modelling studies.

Guanylthiourea (GTU) derivatives were identified as possible anti-malarial agents, recently, using in vitro studies on Plasmodium falciparum. This article gives an account of the in vivo anti-malarial activity of GTU derivatives against experimental rodent malaria. A total of 20 synthesized GTU derivatives were evaluated for in vivo antimalarial activity, out of which six showed encouraging results; one compound appeared to have curative potential. Molecular docking and molecular dynamics analysis were carried out to understand the molecular level interactions.

Design and synthesis of guanylthiourea derivatives as potential inhibitors of Plasmodium falciparum dihydrofolate reductase enzyme.

A new class of compounds based on S-benzylated guanylthiourea has been designed as potential PfDHFR inhibitors using computer aided methods (molecular electrostatic potential, molecular docking). Several compounds in this class have been synthesized starting from guanylthiourea and alkyl bromides. In vitro studies showed that two compounds from this class are active with the IC50 value of 100 µM and 400 nM.

Antihypoxic and antioxidant effects of exogenous succinic acid and aminothiol succinate-containing antihypoxants.

Pronounced antihypoxic and antioxidant effects of preventive injection of succinic acid, aminothiol antihypoxants gutimine and amtizol, and succinate-containing aminothiol antihypoxants gutimine succinate and amtizol succinate to Wistar rats with acute hypoxic hypoxia have been demonstrated. Exogenous succinic acid was inferior to aminothiol compounds by antihypoxic effect, but superior to them by its effect on the level of LPO products. Succinate in the aminothiol molecule modulated the intensity of their antihypoxic and antioxidant effects. It did not modulate the antihypoxic activity of amtizol, but reduced the antihypoxic effect of gutimine, presumably because of the physicochemical characteristics of aminothiols. Comparison of the intensities of antihypoxic and antioxidant effects of the studied drugs showed no direct relationship between these effects.

Electronic structure and reactivity of guanylthiourea: a quantum chemical study.

Electronic structure analysis of guanylthiourea (GTU) and its isomers has been carried out using quantum chemical methods. Two major tautomeric classes (thione and thiol) have been identified on the potential energy (PE) surface. In both the cases conjugation of pi-electrons and intramolecular H-bonds have been found to play a stabilizing role. Various isomers of GTU on its PE surface have been analyzed in two different groups (thione and thiol). The interconversion from the most stable thione conformer (GTU-1) to the most stable thiol conformer (GTU-t1) was found to take place via bimolecular process which involves protonation at sulfur atom of GTU-1 followed by subsequent C-N bond rotation and deprotonation. The detailed analysis of the protonation has been carried out in gas phase and aqueous phase (using CPMC model). Sulfur atom (S1) was found to be the preferred protonation site (over N4) in GTU-1 in gas phase whereas N4 was found to be the preferred site of protonation in aqueous medium. The mechanism of S-alkylation reaction in GTU has also been studied. The formation of alkylated analogs of thiol isomers (alkylated guanylthiourea) is believed to take place via bimolecular process which involves alkyl cation attack at S atom followed by C-N bond rotation and deprotonation. The reactive intermediate RS(NH(2))C-N-C(NH(2))(2)(+) belongs to the newly identified [symbol: see text]N(<--L)(2) class of species and provides the necessary dynamism for easy conversion of thione to thiol.

[Neurophysiological analysis of the effects of antihypoxic versus psychotropic agents]. / Neirofiziologicheskii analiz deistviia antigipoksantov v sravnenii s psikhotropnymi sredstvami.

The Fourie EEG spectral analysis of thr sensomotor cortex and dorsal hypocampus in freely moving rats could reveal the common pharmacological EEG effects of different antihypoxic agents (gutimin, amtizole, emoxipine, and 3-OPK). All the agents decreased the total EEG power (they all reduced the absolute power in all frequency bands) and simultaneously enhanced (2 relative power. The former suggests that there was a decrease in the energetic level of bioelectric fluctuations, which may indicate that the brain reduces its energetic functioning level. The latter means that antihypoxic drugs activate the central nervous system. This effect may normalize EEG activity during hypoxic conditions, which causes the enhancement of slow-wave activity and reduces fast EEG activity. The pharmacological EEG effects of different groups of psychotropic drugs (nootropic drugs, psychostimulants, antidepressants, benzodiazepine tranquilizers, etc.) versus antihypoxants are discussed.

[Antihypoxants: their status and outlook]. / Antigipoksanty: sostoianie i perspektivy.

The survey deals with the up-to-date information in the literature on the problem of pharmacological correction of pathological changes found in the organism in the hypoxic syndrome. The principal approaches to pharmacotherapy of this pathological condition are pointed out. Information on the up-to-date and effective antihypoxia agents applied in medical practice and those in the stage of development is given.

[Antihypoxants in emergency medicine]. / Antigipoksanty v neotlozhnoi meditsine.

Presents the results of many-year experimental studies, clinical trials, and medical use of drugs of a new pharmacological class: antihypoxants. Antihypoxants are perspective drugs of urgent medicine, which was demonstrated on various models (all types of hypoxia, myocardial, brain, renal, and liver ischemia, grave mechanical and thermal injuries, blood loss, etc.) and in patients with these states.

[Role of hypoxia factor in changes of ionic composition of blood and muscle tissue in experimental botulinum poisoning]. / Rol' gipoksicheskogo faktora v izmenenii ionnogo sostava krovi i myshechnoi tkani pri éksperimental'noi botulinicheskoi intoksikatsii.

Levels of sodium and potassium ions in muscle tissue, blood plasma and red cells were measured, and the index characterizing the capacity of tissue to accumulate cations from the environment and the discrimination coefficient were calculated in experiments on white rats subjected to experimental generalized botulinum poisoning. Late stages of botulism were found to involve a deficit of potassium and sodium ions in red cells. With the progress of intoxication, a deficit of potassium ions develops in muscle tissue and the capacity of this tissue to accumulate potassium ions from the environment declines. All these disorders are more expressed in rapidly contracting skeletal muscles. An antihypoxant gutimin reduces sodium deficit in the blood plasma and red cells and leads to normalization of potassium ion levels in muscle tissue.

[The effect of gutimine and amtizol on the K, Na-pump activity of the nerve cell]. / Vliianie gutimina i amtizola na aktivnost' K, Na-nasosa nervnoi kletki.

The antihypoxants gutimine and amtisole, its cyclic derivative of 3.5-diamino-1,thia-2,4-diazole were tested for their effects on the activity of one of the most power-consuming functions of a nerve cell--on the activity of the K, Na-pump during normoxia. Gutimine was found to decrease K, Na-pump activity in the Retzius neurone by an average of 70% presumably due to its inhibitory effects of leakage currents. The experiments suggest that the preventive protective effect of gutimine is displayed at the membranous level. Amtisole was found to unchange the functional activity of the K, Na-pump in the Retzius neurone.

[The use of sodium gamma-oxybutyrate and gutimine for decreasing metabolic disorders in the heart, caused by exotoxic shock in acetic acid poisoning]. / Primenenie gamm-oksibutirata natriia i gutimina dlia umen'sheniia metabolicheskikh narushenii v serdtse, vyzvannykh ékzotoksicheskim shokom pri otravlenii ukusnoi kislotoi.

Exotoxic shock was simulated in non-linear rat males anesthetized with barbital after intragastric administration of 70% acetic acid at a dose of 4 ml/kg using a gastric tube. Energy metabolism and the rate of lipid peroxidation were studied in heart muscle during the decompensated and terminal periods of exotoxic shock. Sodium hydroxybutyrate (200 mg/kg) and gutimine (75 mg/kg), administered alone within 30 min after the poisoning, prolonged the period before manifestation of the decompensated and terminal steps of the shock; these drugs decreased the rate of metabolic impairments in the myocardium by decreasing the rates of adenine nucleotide catabolism, of glycolysis, lipolysis and lipid peroxidation.

[Effect of using gutimine in the pre-ischemic period on myocardial phospholipids during reperfusion]. / Vliianie primeneniia gutimina v predyshemicheskom periode na fosfolipidy miokarda vo vremia reperfuzii.

Physico-chemical properties of phospholipids were studied in heart muscle at postischemic period after preventive treatment with gutimine. Two administrations of the drug, as compared with its three times treatment, during the preischemic period contributed to development of stable adaptive antiischemic and antireperfusion responses involving alterations in fatty acid composition of phospholipids as demonstrated by an increase in content of arachidonic acid in all the phospholipid fractions studied as well as in total content of monoenic acids in lysophosphatidyl choline and phosphatidyl serine and of polyenic acids in lysophosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine.

Immune response developing in tumorous organism as a result of immunotherapy. Chance of recovery?

S-allylgutimine has immunostimulant and tumor cell inhibitory activities. This complex action may be a result of the stimulation of IL-2 production. The effectiveness of immunotherapy depends on the uncoupling of IL-2 downregulation. This principle can be widely used with those immunological diseases where IL-2 level is decreased through downregulation. The Kokonov reaction, which was used originally to indicate tumors, is presumably a marker of immunoreactivity. According to one hypothesis no specific antigen can be found on the surface of neoplastic cells but another type, 'weak antigen' appears, which originates from the alteration of a cell surface glycoprotein beta 1-6 saccharide chain branching that is directly related to the increased immune reactivity. The inhibition of downregulation enhances the elimination of neoplastic cells whose membrane surface glycoproteins are altered.

Pathogenesis and pharmacorrection of early postresuscitation cardiac arrhythmia.

Effect of acute lethal blood loss on character and frequency of cardiac arrhythmias in postresuscitation period has been studied. Experiments were carried out on mongrel male rats resuscitated after 4- and 6-min clinical death caused by acute blood loss. Electric cardiac instability was found in early postresuscitation period. Pacemaker migration, paroxysmal ventricular tachycardia, blockades and extrasystole that lead to ventricular fibrillation were observed in 20 percent of cases. Supported by correlative analysis it has been established that the main arrhythmogenic factors are abundance of catecholamines, free fatty acids, dienic conjugates, lactate and inhibition of Ca dependent ATPase. Antiarrhythmogenic effects of antihypoxant gutimin, the beta-adrenoreceptor blocker inderal, antioxidant oxypiridin-6 were noticed after their separate administration before clinical death. The same effect of carnosine and phosphocreatine administered during resuscitation also was noticed.

[An electromyographic method for determining the antihypoxic activity of preparations]. / Elektromiograficheskii metod opredeleniia protivogipoksicheskoi aktivnosti preparatov.

To measure drug antihypoxic activity, an electromyographic method was worked out. The main idea of the method is to estimate the influence of these substances on the amplitude of slow electric waves of smooth muscles on an isolated strip of rat small intestine in situ. This parameter whose value directly depends on tissue pO2 was recorded under the conditions of artificial ischemia of the intestinal strip. Circulatory hypoxia was simulated by the clamping of mesentery vessels, and the time was determined, during which the amplitude of slow electric waves reduced to 1/3 of the initial value in control animals and rats treated beforehand with the drugs under study. Antihypoxic activity of the drugs was calculated as difference in these time intervals between experiment and control, given in per cent.

[The action of amtizol and gutimin on the respiratory metabolism of the neuron]. / Deistvie amtizola i gutimina na dykhatel'nyi metabolizm neirona.

The effects of antihypoxants gutimine and amtisole on oxygen consumption by the intact nerve cell of the invertebrate and the activity of NADN-DH and SDH-dependent ways of oxidation in the cell were studied. Under normoxia gutimine inhibited the nerve cell respiration and decreased the activity of NADN-DN and SDH-dependent ways of oxidation by 15% and 5% respectively. Amtisole activated the neuron respiration increasing the activity of NADN-DH-dependent way of oxidation. Both antihypoxants, despite the fact that they refer to the same class of compounds, have different mechanisms of action on the neuron metabolism. Gutimine appears to be a pharmacological agent, protector, amtisole as an initiator of the active adaptative reorganization of the intracellular metabolism.

[Ultrastructural features of heart insufficiency and its correction during the post-asphyxia period]. / Ul'trastrukturnye priznaki serdechnoi nedostatochnosti i ee korrektsiia v postasfiksicheskom periode.

The ultrastructure of myocardium was studied in the experiments on rats during 24 hours after 6-min mechanical asphyxia with following clinical death. It has been established that the contractile cardiac apparatus of myocytes lesions on the intracellular edema background is the main while energy production process impairs insignificantly. The effectiveness of anti-hypoxia, membrane stability and protease inhibiting preparations for prevention of postresuscitation myocardium lesion was examined. The contrykal protective action, suppressing the proteolytic ferment hyperactivity was determined.

[Effect of pharmacologic preparations on the electrical activity of cerebellar slices under hypoxia]. / Vliianie nekotorykh farmakologicheskikh preparatov na élektricheskuiu aktivnost' srezov mozzhechka v usloviiakh gipoksii.

The effects of some antihypoxants (piracetam, GABA, sodium hydroxybutyrate and gutimine) on the electrical activity of the cerebellar neurons (Purkinje cells) of rats and mice were studied in the surviving slices under normoxia and increasing hypoxia. All the agents were found to produce phase changes in the base-line electrical activity of neurons: alternation of hyperexcitation and inhibition. Under hypoxia GABA and sodium hydroxybutyrate exerted the direct protective action on neuron metabolism supporting its electrogenic function. In the in vitro conditions in contrast to in situ conditions gutimine was shown to behave as a prohypoxant. The possibility of using the brain slices as the test system to study the mechanisms of action of the agents and the prognostic criterion during selection of prohypoxants is discussed.