Synthesis, pharmacological screening and computational analysis of some 2-(1H-Indol-3-yl)-N'-[(un)substituted phenylmethylidene] acetohydrazides and 2-(1H-Indol-3-yl)-N'-[(un)substituted benzoyl/2-thienylcarbonyl]acetohydrazides.

The undertaken research was initiated by transforming 2-(1H-Indol-3-yl)acetic acid (1) in catalytic amount of sulfuric acid and ethanol to ethyl 2-(1H-Indol-3-yl)acetate (2), which was then reacted with hydrazine monohydrate in methanol to form 2-(1H-Indol-3-yl)acetohydrazide (3). Further, The reaction scheme was designed into two pathways where, first pathway involved The reaction of 3 with substituted aromatic aldehydes (4a-o) in methanol with few drops of glacial acetic acid to generate 2-(1H-Indol-3-yl)-N'-[(un)substitutedphenylmethylidene]acetohydrazides (5a-o) and in second pathway 3 was reacted with acyl halides (6a-e) in basic aqueous medium (pH 9-10) to afford 2-(1H-Indol-3-yl)-N'-[(un)substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides (7a-e). All The synthesized derivatives were characterized by IR, EI-MS and 1H-NMR spectral techniques and evaluated for their anti-bacterial potentials against Gram positive and Gram negative bacterial strains and it was found that compounds 7a-d exhibited antibacterial activities very close to standard Ciprofloxacin. The synthesized derivatives demonstrated moderate to weak anti-enzymatic potential against α-Glucosidase and Butyrylcholinesterase (BChE) where, compounds 7c and 5c exhibited comparatively better inhibition against these enzymes respectively. Compounds 7a, 7d and 7e showed excellent anti-enzymatic potentials against Lipoxygenase (LOX) and their IC50 values were much lower than the reference standard Baicalein. Enzyme inhibitory activities were also supported by computational docking results. Compounds 5c, 7a, 7b and 7c also showed low values of % hemolytic activity as well, showing that these molecules were not toxic, indicating that these molecules can be utilized as potential therapeutic agents against inflammatory ailments.

A Survey of Practice and Knowledge of Refugee and Migrant Pregnant Mothers Surrounding Neonatal Jaundice on the Thailand-Myanmar Border.

BACKGROUND: In populations with a high prevalence of glucose-6-phosphate dehydrogenase deficiency, practices that can induce haemolysis need to be identified to raise awareness of preventable risks. The aim of this survey was to determine the proportion of prospective mothers using haemolytic agents and their knowledge and practice surrounding neonatal jaundice. METHODS: Pregnant mothers were invited to participate in a cross-sectional survey conducted at Shoklo Malaria Research Unit on the Thailand-Myanmar border. RESULTS: From 12 April 2015 to 12 June 2015, 522 pregnant women completed the survey. Mothball use in the household was reported by 41.4% (216 of 522) of prospective mothers and menthol containing products on baby skin by 46.7% (244 of 522). CONCLUSION: Just over 40% of the households reported use of naphthalene-containing mothballs. Future health promotion activities that focus on reducing naphthalene mothball and menthol-containing products use have the potential to reduce rates of severe neonatal jaundice in this population.

Optimization of phenylhydrazine induced hyperbilirubinemia in experimental rabbit.

Induction of hyperbilirubinemia in experimental rabbits by phenylhydrazine was optimized in terms of dose, dose interval and number of doses using response surface methodology. Central Composite Design was employed using five levels for each of the three input variables. Degree of hyperbilirubinemia was measured in terms of bilirubin level in serum of animals. A dose dependent significant elevation (P<0.05) of total serum bilirubin level was observed which was optimized by using eight factorial, six axial and six central points as suggested by experimental design. Optimum levels of phenylhydrazine dose, total number of doses and a dose interval to achieve maximum elevation (4.06 mg/dl-1) of total serum bilirubin were found to be 11.56 mg/kg-1 body weight, 8 and 24.65 h, respectively. The induction procedure was validated by performing five replicate experiments on a group of five animals which showed 3.56 ± 0.47 mg/kg-1 body weight elevation in total serum bilirubin level.

[Balance between cardiovascular pharmacological and hemolytic effects of saponins of Panax notogenseng].

PNS (total saponins of Panax notognseng, PNS) has a clear effect and wide application prospect for cardiovascular diseases. At the same time, saponins have hemolytic properties, which are related to its molecular structure type and dosage. On one hand, this article summarizes the research progress of PNS in heart cerebrovascular pharmacology pharmacological in recent five years, a number of studies both in vitro and in vivo for overall body, organs, cells and molecules, show that PNS could improve myocardial and cerebral ischemia injury, and it has effects in resisting thrombosis, inflammation, oxidation, atherosclerosis, and modulating vascular endothelial cells function and improving the cerebral ischemia injury etc. On the other hand, the hemolysis effect of PNS is closely related to its molecular structure type and administrating dosage. Different structures bring about different hemolysis activities. Structure-activity relationship suggests that the length of sugar side chains attached to C-20 and the disaccharide connection mode on C-3 may influence the hemolysis activity of PNS. Within the dose range from 2.5 to 250 mg•L⁻¹, PNS has no hemolysis activity. However, PNS exhibits hemolytic properties at high concentrations(≥500 mg•L⁻¹). Based on the hemolytic or anti-hemolysis characteristics of saponins, and dose-response relationship, the rational clinical application of PNS can be guaranteed by controlling the ratio of hemolytic monosaponins in PNS and improving the hemolytic test method.

An in vivo drug screening model using glucose-6-phosphate dehydrogenase deficient mice to predict the hemolytic toxicity of 8-aminoquinolines.

Anti-malarial 8-aminoquinolines drugs cause acute hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDD). Efforts to develop non-hemolytic 8-aminoquinolines have been severely limited caused by the lack of a predictive in vivo animal model of hemolytic potential that would allow screening of candidate compounds. This report describes a G6PDD mouse model with a phenotype closely resembling the G6PDD phenotype found in the African A-type G6PDD human. These G6PDD mice, given different doses of primaquine, which used as a reference hemolytic drug, display a full array of hemolytic anemia parameters, consistently and reproducibly. The hemolytic and therapeutic indexes were generated for evaluation of hemotoxicity of drugs. This model demonstrated a complete hemolytic toxicity response to another known hemolytic antimalarial drug, pamaquine, but no response to non-hemolytic drugs, chloroquine and mefloquine. These results suggest that this model is suitable for evaluation of selected 8-AQ type candidate antimalarial drugs for their hemolytic potential.

Hematotoxicity and genotoxicity of mercuric chloride following subchronic exposure through drinking water in male rats.

Erythrocytes are a convenient model to understand the subsequent oxidative deterioration of biological macromolecules in metal toxicities. The present study examined the variation of hematoxic and genotoxic parameters following subchronic exposure of mercuric chloride via drinking water and their possible association with oxidative stress. Male rats were exposed to 50 ppm (HG1) and 100 ppm (HG2) of mercuric chloride daily for 90 days. A significant dose-dependent decrease was observed in red blood cell count, hemoglobin, hematocrit, and mean cell hemoglobin concentration in treated groups (HG1 and HG2) compared with controls. A significant dose-dependent increase was observed in lipid peroxidation; therefore, a significant variation was found in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase. Interestingly, mercuric chloride treatment showed a significant dose-dependent increase in frequency of total chromosomal aberration and in percentage of aberrant bone marrow metaphase of treated groups (p < 0.01). The oxidative stress induced by mercury treatment may be the major cause for chromosomal aberration as free radicals lead to DNA damage. These data will be useful in screening the antioxidant activities of natural products, which may be specific to the bone marrow tissue.

Unsuspected glucose-6-phosphate dehydrogenase deficiency presenting as symptomatic methemoglobinemia with severe hemolysis after fava bean ingestion in a 6-year-old boy.

We report the occurrence of symptomatic methemoglobinemia in a previously healthy boy, who presented with severe acute hemolysis after fava bean ingestion. The methemoglobinemia revealed a previously unrecognized glucose-6-phosphate dehydrogenase (G6PD) deficiency. We discuss the pathophysiology of severe methemoglobinemia when associated with acute hemolysis, favism, and the common African G6PD A-variant [G6PD, VAL68MET, ASN126ASP]. In conclusion, screening for G6PD deficiency must be considered in symptomatic methemoglobinemia, especially in young boys, when associated with intravascular hemolysis.

Free radical scavenging, cytotoxic, and hemolytic activities of an active antioxidant compound ethyl gallate from leaves of Acacia nilotica (L.) Wild. Ex. Delile subsp. indica (Benth.) Brenan.

UNLABELLED: In the present study, free radical scavenging, cytotoxic, and hemolytic activities of the polyphenolic compound ethyl gallate isolated from ethanol extract of Acacia nilotica Wild. Ex. Del. leaves were determined. The free radical-scavenging activities of the ethyl gallate were demonstrated in several in vitro assays in order to evaluate the possible antioxidant mechanism. The results revealed ethyl gallate as hydrogen donor, metal chelator, and free radical scavenger. Ethyl gallate was effective in scavenging 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals and the IC50 value was lower than all the positive controls used in this study. Deoxyribose degradation assay revealed that ethyl gallate had more iron-chelating ability than the direct hydroxyl radical-scavenging ability. The results of the cytotoxic study revealed that the compound was moderately active and IC50 value was found to be >100 µg/mL for Vero cell lines and 72 µg/mL for Hela cell lines. The compound possessed no hemolytic activity against rat and human erythrocytes revealing its cytotoxic mechanism and nontoxicity. The results from this work will provide an important information for the food and pharmacological industries with respect to the use of the compound as an antioxidant and a health-related drug. PRACTICAL APPLICATION: Antioxidant from plant sources is safe to use, as compared to synthetic products. It also can be used as a supplement to alleviate most of the diseases because of its free radical-scavenging activity.

Antitrypanosomal activity of a diterpene and lignans isolated from Aristolochia cymbifera.

Bioguided fractionation of extract from the leaves of Aristolochia cymbifera led to the isolation of the furofuran lignans fargesin, epieudesmin, and sesamin; the dibenzylbutyrolactone lignans hinokinin and kusunokinin; and an ENT-labdane diterpene named copalic acid. Our data demonstrated that copalic acid and kusunokinin were the most active compounds against trypomastigotes of Trypanosoma cruzi. Additionally, copalic acid demonstrated the highest parasite selectivity as a result of low toxicity to mammalian cells, despite a considerable hemolytic activity at higher concentrations. Among the isolated compounds, kusunokinin could be considered the most promising candidate, as it displayed significant activity against intracellular amastigotes (IC(50) = 17 µM) and trypomastigotes (IC(50) = 51 µM) without hemolytic activity. Fargesin, hinokinin, epieudesmin, and sesamin were also effective against trypomastigotes, but these compounds were highly toxic to mammalian cells and no parasite selectivity could be identified. The need for novel drugs for American trypanosomiasis is evident, and these secondary metabolites from A. cymbifera represent a useful tool for drug design.

Preparation and characterization of dextran nanobubbles for oxygen delivery.

Dextran nanobubbles were prepared with a dextran shell and a perfluoropentan core in which oxygen was stored. To increase the stability polyvinylpirrolidone was also added to the formulation as stabilizing agent. Rhodamine B was used as fluorescent marker to obtain fluorescent nanobubbles. The nanobubble formulations showed sizes of about 500nm, a negative surface charge and a good capacity of loading oxygen, no hemolytic activity or toxic effect on cell lines. The fluorescent labelled nanobubbles could be internalized in Vero cells. Oxygen-filled nanobubbles were able to release oxygen in different hypoxic solutions at different time after their preparation in in vitro experiments. The oxygen release kinetics could be enhanced after nanobubble insonation with ultrasound at 2.5MHz. The oxygen-filled nanobubble formulations might be proposed for therapeutic applications in various diseases.

A new animal model of hemolytic hyperbilirubinemia-induced bilirubin encephalopathy (kernicterus).

Neonatal hyperbilirubinemia can cause bilirubin encephalopathy (kernicterus). Spontaneously jaundiced (jj) Gunn rats treated with sulfonamide (sulfa) to displace bilirubin from serum albumin, develop bilirubin encephalopathy and abnormal brainstem auditory evoked potentials (BAEPs) comparable with human newborns. We hypothesized phenylhydrazine (PHZ)-induced hemolysis would significantly elevate total plasma bilirubin (TB) in jj Gunn rat pups and produce BAEP abnormalities similar to those observed after sulfa. PHZ 0, 25, 50, or 75 mg/kg was administered intraperitonealy to 15-d-old jjs. An initial TB was recorded in each animal, and a second recorded 1-4 d postinjection to generate a dose-response curve. After PHZ 75 mg/kg, TB peaked at about 30 mg/dL at 48-72 h. A second group of jjs injected with PHZ (0, 25, 50, or 75 mg/kg) and nonjaundiced controls given PHZ 75 mg/kg had HCT and TB at baseline, and HCT, TB, and BAEPs recorded at 48 h. BAEP wave II and III amplitudes decreased, and I-II and I-III interwave intervals increased indicating abnormal central (brainstem) auditory function. PHZ-induced hemolysis in jaundiced Gunn rat pups produces sufficiently elevated TB levels to produce bilirubin encephalopathy. This new model may be a more clinically relevant experimental model of kernicterus- and bilirubin-induced neurologic disorders.

[Hemolytic uremic syndrome (HUS). An up-dated nosological classification]. / Síndrome urémico hemolítico. Ubicación nosológica actual.

An up-date of the causes and pathogenesis of the HUS is reported. After more than 40 years of research we are able to define the infectious agents and the toxin involved. The mechanisms and the molecules involved in the non-diarrheal (atypical) entities producing HUS have also been characterized. This new situation allows us to develop a diagnostic algorithm that enables us to better define preventive and therapeutic measures, based on more rational evidence.

Sindrome uremico hemolitico: ubicación nosologica actual / Hemolytic uremic syndrome (HUS): an up-dated nosological classification

An up-date of the causes and pathogenesis of the HUS is reported. After more than 40 years of research we are able to define the infectious agents and the toxin involved. The mechanisms and the molecules involved in the non-diarrheal (atypical) entities producing HUS have also been characterized. This new situation allows us to develop a diagnostic algorithm that enables us to better define preventive and therapeutic measures, based on more rational evidence.