phenanthrenes and Hemolysis

Halofantrine is an antimalarial drug which is widely prescribed for the treatment of infections with chloroquine-resistant strains of Plasmodium falciparum. Chemically, it is a phenanthrene methanol, belonging to the aryl-amino-alcohol family. It has recently been recognized that this drug may induce rare but serious, cardiotoxic effects, including lengthening of the QTc interval, 'torsade de pointes' and induction of late ventricular potentials. These events are thought to be related to a quinidine-like action of the drug. In addition, severe haemolytic accidents have been reported, mimicking blackwater fever and indicating an immunological process. As a result of these side-effects, new guidelines for prescription and more cautious use of halofantrine, particularly as a stand-by treatment for febrile access among travellers, are required.

Topics: Antimalarials; Electrocardiography; Heart Diseases; Hemolysis; Humans; Malaria, Falciparum; Phenanthrenes; Prospective Studies

Halofantrine is an antimalarial drug widely prescribed for chloroquine-resistant strains of Plasmodium falciparum. It has been recognized to cause serious deleterious effects which have dampened early enthusiasm for this compound. Basically, the adverse effects involve lengthening of the QTc interval, torsade de pointes and induction of late ventricular potentials. These side effects are related to the quinidine-like effect of the drug which has a chemical structure similar to quinine and quinidinic drugs. More recently, severe haemolytic accidents have been reported suggesting an autoimmunization mechanism. These side effects imply new rules for prescription and more prudent use of halofantrine, especially for prophylaxic therapy against malarial attacks in travellers.

Topics: Antimalarials; Drug Prescriptions; Heart; Heart Diseases; Hemolysis; Humans; Phenanthrenes

Streptococcus suis is a highly zoonotic pathogen that is a serious threat to human health and the development of the pig industry worldwide. The virulence factors produced during S. suis infection play an important role, and the pore-forming activity of suilysin is considered an important virulence-related factor, especially in meningitis. Treatment of S. suis infection with traditional antibiotics is becoming increasingly challenging due to bacterial resistance. The purpose of this study is to verify the role of cryptotanshinone in the process of S. suis infection and provide a new drug precursor for the treatment of S. suis infection.. In this study, we used circular dichroism spectroscopy to demonstrate that cryptotanshinone alters the secondary structure of suilysin. The results of the antibacterial activity and haemolysis assays showed cryptotanshinone could inhibit the pore-forming activity of suilysin without affecting bacterial growth or its expression. We also showed that cryptotanshinone reduces bacterial damage and penetration in vitro, reduce the S. suis-induced inflammatory response and provide protection against bacterial infections in vivo and in vitro.. Cryptotanshinone is a potential compound precursor for treating S. suis infection.. Cryptotanshinone may be a promising leading compound for S. suis infection and related diseases.

Topics: Animals; Anti-Bacterial Agents; Hemolysin Proteins; Hemolysis; Humans; Inflammation; Mice; Phenanthrenes; Protein Structure, Secondary; Streptococcal Infections; Streptococcus suis; Virulence; Virulence Factors

Chemical investigation and activity test of Arundina graminifolia led to the isolation of six phenanthrenes: blestriarene A (1), shancidin (2), densiflorol B (3), ephemeranthoquinone (4), coelonin (5) and lusianthridin (6). The isolated compounds demonstrated antibacterial and anti-haemolytic activities. It was found that compounds 1 and 2 had medium antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli, with MICs of 20-40 μg/mL and MBCs of 40-320 μg/mL. Bactericidal mechanisms were explored. Rupture of cell wall and membrane and leakage of nuclear mass were observed by transmission electron microscopy (TEM). Moreover, compounds 1-3 attenuated the erythrocyte damage. Compounds 1 and 2 showed significant anti-haemolytic activity with inhibition rate about 50% at 16 μg/mL.

Topics: Animals; Anti-Bacterial Agents; Bacillus subtilis; Drug Evaluation, Preclinical; Erythrocytes; Escherichia coli; Hemolysis; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Molecular Structure; Orchidaceae; Phenanthrenes; Rabbits; Staphylococcus aureus

Juncunol is a phenanthrene isolated from the halophyte species Juncus acutus, with selective cytotoxic activity towards human hepatocarcinoma (HepG2) cells. However, its mechanism of action is unknown.. The in vitro cytotoxic mechanism of juncunol was evaluated on HepG2 cells through several methods to elucidate its potential to induce apoptotic features, decrease mitochondrial membrane potential, promote internal ROS production and influence cell cycle. We also report its haemolytic activity on human erythrocytes and in silico DNA-binding studies.. Juncunol reduced HepG2 cells proliferation through the induction of apoptotic cellular death, in a concentration-dependent manner. Apoptosis induction seems to be related with a decrease of the mitochondrial membrane potential but not with ROS production. Juncunol had no haemolytic activity and may act as a DNA intercalator. Our data suggests juncunol as a suitable candidate for more detailed studies, including in vivo experiments, in order to completely characterize its mode of action.

Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Computer Simulation; Dose-Response Relationship, Drug; Hemolysis; Humans; In Vitro Techniques; Liver Neoplasms; Membrane Potential, Mitochondrial; Molecular Docking Simulation; Phenanthrenes; Reactive Oxygen Species

Bletillae Rhizoma, the tuber of Bletilla striata, has been used in Chinese traditional medicine to treat infectious diseases. Chemical studies indicated that phenanthrene was one of the most important components of the herb, with a broad spectrum of antibiotic activity against Gram-positive bacteria. The objective of this study was to further characterize the antibacterial activity of the phenanthrene fraction from the fibrous root of the pseudobulb of B. striata.. The phenanthrene fraction (EF60) from the ethanol extract of fibrous roots of Bletilla striata pseudobulbs was isolated using polyamide column chromatography. The antibacterial activity of the fraction was evaluated in vitro using a 96-well microtiter plate and microbroth dilution method. The cytotoxicity of EF60 against mammalian cells was tested by hemolysis and MTT assays.. Our studies indicated that EF60 is worthy of further investigation as a potential phytotherapeutic agent for treating infections caused by S. aureus and MRSA.

Topics: Anti-Bacterial Agents; Cytotoxins; Drugs, Chinese Herbal; Hemolysis; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Orchidaceae; Phenanthrenes; Plant Roots; Staphylococcus aureus

Topics: Antimalarials; Child; Child, Preschool; Hemolysis; Humans; Malaria; Male; Nigeria; Phenanthrenes; Risk Factors

Amphiphiles which induce either spiculated (echinocytic) or invaginated (stomatocytic) shapes in human erythrocytes, and ionophore A23187 plus Ca(2+), were studied for their capacity to induce shape alterations, vesiculation and hemolysis in the morphologically and structurally different lamprey and trout erythrocytes. Both qualitative and quantitative differences were found. Amphiphiles induced no gross morphological changes in the non-axisymmetric stomatocyte-like lamprey erythrocyte or in the flat ellipsoidal trout erythrocyte, besides a rounding up at higher amphiphile concentrations. No shapes with large broad spicula were seen. Nevertheless, some of the 'echinocytogenic' amphiphiles induced plasma membrane protrusions in lamprey and trout erythrocytes, from where exovesicles were shed. In trout erythrocytes, occurrence of corrugations at the cell rim preceded protrusion formation. Other 'echinocytogenic' amphiphiles induced invaginations in lamprey erythrocytes. The 'stomatocytogenic' amphiphiles induced invaginations in both lamprey and trout erythrocytes. Surprisingly, in trout erythrocytes, some protrusions also occurred. Some of the amphiphiles hemolyzed lamprey, trout and human erythrocytes at a significantly different concentration/membrane area. Ionophore A23187 plus Ca(2+) induced membrane protrusions and sphering in human and trout erythrocytes; however, the lamprey erythrocyte remained unperturbed. The shape alterations in lamprey erythrocytes, we suggest, are characterized by weak membrane skeleton-lipid bilayer interactions, due to band 3 protein and ankyrin deficiency. In trout erythrocyte, the marginal band of microtubules appears to strongly influence cell shape. Furthermore, the presence of intermediate filaments and nuclei, additionally affecting the cell membrane shear elasticity, apparently influences cell shape changes in lamprey and trout erythrocytes. The different types of shape alterations induced by certain amphiphiles in the cell types indicates that their plasma membrane phospholipid composition differs.

Topics: Abietanes; Animals; Anion Exchange Protein 1, Erythrocyte; Calcimycin; Calcium; Carboxylic Acids; Cell Size; Chlorpromazine; Cytoskeleton; Detergents; Diterpenes; Erythrocytes; Glucosides; Hemolysis; Humans; Ionophores; Lampreys; Phenanthrenes; Polyethylene Glycols; Quaternary Ammonium Compounds; Tissue Fixation; Trout

Topics: Aged; Antimalarials; Chloroquine; Glycogen Storage Disease Type I; Hemolysis; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Phenanthrenes

Topics: Acute Disease; Adolescent; Animals; Antimalarials; Blackwater Fever; Blood; Central African Republic; Hemolysis; Humans; Malaria, Falciparum; Male; Middle Aged; Phenanthrenes; Plasmodium falciparum; Renal Dialysis

Triptolide (Tri) is an active principle of Tripterygium hypoglaucum Hutch, which has been used to treat cancers and autoimmune diseases in folk medicine. The lymphocyte proliferation (LP) induced by Con A or Lipopolysaccharide (LPS) was suppressed by Tri at 50 and 500 ng/ml. At 5 ng/ml the suppressive effect on LP induced by Con A was much stronger than that by LPS. The humoral immune reaction monitored by quantitative hemolysis spectrophotometry (QHS) was suppressed by Tri 0.75 and 1 mg/kg ip. IL-2 production by mouse spleen cells were suppressed by Tri 5, 50,500 ng/ml in vitro and 0.5, 0.75 and 1 mg/kg ip. IL-2 activity was assayed by assessing its ability to support proliferation of selected IL-2-dependent T cell line, measured by colorimetric method which is based on the ability of viable cells to cleave MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide). Ts cells induced by supraoptimal immune (SOI) were suppressed by Tri 0.5 and 0.75 mg/kg ip. These results suggest T or its subpopulations and B lymphocytes may be the target cells of Tri.

Topics: Animals; Cell Division; Diterpenes; Epoxy Compounds; Female; Hemolysis; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Phenanthrenes; T-Lymphocytes

A basic phospholipase A2 (PLA2) enzyme, TFV PL-X (pI 9.2) and two acidic PLA2 enzymes, TFV PL-Ia (pI 4.9) and TFV PL-Ib (pI 4.5) were purified from Trimeresurus flavoviridis venom on CM-Sephadex C-25 and QAE-Sephadex A-25 columns, respectively. The basic enzyme exists as a monomer, whereas the acidic enzymes are dimers. These enzymes differ in properties such as molecular weight, Km, optimum pH and temperature and pharmacological properties. The basic enzyme hydrolysed purified phospholipids in the order of PC greater than PE greater than PS greater than PI = 0, while for TFV PL-Ia and TFV PL-Ib the order was PC greater than PE greater than PS = PI = 0. TFV PL-X was comparatively more toxic, with an LD50 value of 4.2 micrograms/g (i.p.), while the acidic PLA2 enzymes had LD50 values above 8 micrograms/g (i.p.). All three enzymes induced edema when injected into the mouse foot pad. Aristolochic acid, an alkaloid (8-methoxy-6-nitrophenanthro(3,4-d)-1,3-dioxole-5-carboxylic acid) from the medicinal plant Aristolochia radix, interacts with these PLA2 enzymes. It is a competitive inhibitor with varying affinity when PC is used as substrate. Aristolochic acid inhibits direct and indirect hemolytic activity, as well as edema-inducing activity, of TFV PL-X, but fails to neutralize the lethal potency of the enzyme. On the other hand, it inhibits direct and indirect lytic activity of TFV PL-Ia and TFV PL-Ib only at 10-fold higher concentrations and it enhances the edema-inducing activity of these enzymes. Such effects of aristolochic acid indicates that (1) different mechanisms may be involved in the edema-inducing activity of PLA2 enzymes and (2) catalytic and pharmacological sites are separate on the PLA2 molecule.

Topics: Animals; Aristolochic Acids; Biological Assay; Chemical Phenomena; Chemistry; Chromatography, Gel; Edema; Hemolysis; Molecular Weight; Phenanthrenes; Phosphatidylcholines; Phospholipases; Phospholipases A; Phospholipases A2; Viper Venoms

Topics: Angina Pectoris; Animals; Furans; Hemolysis; In Vitro Techniques; Mice; Phenanthrenes; Plant Extracts; Propranolol

Most work on human erythrocyte interaction with drugs and other compounds has been reported on the basis of total concentrations. Total concentrations alone do not reveal numbers of molecules bound per cell, v. This paper emphasizes determination of v and of binding isotherms, in conjunction with changes in cell morphologies and in hypotonic shock behavior as v is varied. Four drugs and five other compounds were studied, with fresh erythrocytes. The principal findings are: (1) the intact erythrocyte engages in two kinds of binding mechanisms, statistical binding and cooperative binding, depending on the compound. In the case of a detergent, dodecylbenzene sulfonate, the binding is nearly quantitative. (2) The compounds often induce considerable protection against hypotonic hemolysis. However, the binding levels at which maximum protection occurs are rather close to the levels, vL, that occur upon complete conversion to the first distorted morphology. Therefore, the maximally protected erythrocyte may be a distorted erythrocyte. (3) The value n is the apparent total number of sites from Scatchard plotting for compounds which bind in a statistical manner. Levels vp and vw characterize maxima in cooperative binding behavior, also from Scatchard plotting of the data. Despite the wide diversity of over-all levels at which compounds exert their effects, the critical binding levels of and numbers of sites fall into a narrow range:n, vL, vP, and vw are all between 1 and 8 times 10-7 molecules or sites per cell. Most of our data, and that from some other laboratories, indicate that about 2 plus and minus 1 times 10-7 sites per erythrocyte are available for compound binding by the intact cell. Beyond that level, the cell in suspension almost always will be forced into the first obvious morphology change, as seen by phase contrast microscopy. (4) Once stoichiometries are established, the total binding capacity of erythrocytes for such compounds, in blood, can be estimated. An intruding organic molecule would encounter about 6 times as many plasma albumin sites as erythrocyte sites, if the plasma albumin sites were free. However, because albumin in vivo usually forms a complex with one to two fatty acids, the erythrocyte itself is rather likely to act as a transport particle for such compounds.

Topics: Binding Sites; Chlorpromazine; Erythrocytes; Hemolysis; Humans; Kinetics; Mathematics; Methylene Blue; Microscopy, Phase-Contrast; Osmolar Concentration; Phenanthrenes; Propranolol; Quinine; Salicylates

Topics: 17-Ketosteroids; Acetates; Alcohols; Androstanes; Animals; Benzoates; Butyrates; Carboxylic Acids; Chemical Phenomena; Chemistry; Erythrocytes; Esters; Glycyrrhiza; Hemolysis; In Vitro Techniques; Lactates; Methanol; Phenanthrenes; Phthalic Acids; Plants, Medicinal; Propionates; Rats; Saponins; Spirostans; Structure-Activity Relationship; Succinates

Topics: Acids; Animals; Binding Sites; Complement Inactivator Proteins; Guinea Pigs; Hemolysis; Humans; Maleates; Phenanthrenes