Permeability alterations and antihaemolysis induced by amphiphiles in human erythrocytes

Isomaa, Boris; Hägerstrand, Henry; Paatero, Gun I.L.; Engblom, Ann Christine

doi:10.1016/0005-2736(86)90548-1

Cited by 110 publications

(54 citation statements)

References 50 publications

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“…For neutral amphiphiles, no clear structure-activity relationships have emerged. Moreover, amphiphiles at low (sublytic) concentrations protect erythrocytes against hypotonic hemolysis (17,19). The incorporation of amphiphiles into the erythrocyte membrane was also observed directly by using radioactive tracers (14).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Plasmodium falciparum Drug Sensitivity Assay: Inhibition of Parasite Growth by Incorporation of Stomatocytogenic Amphiphiles into the Erythrocyte Membrane

Ziegler

Christensen

Hviid

et al. 2002

Antimicrob Agents Chemother

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Lupeol, which shows in vitro inhibitory activity against Plasmodium falciparum 3D7 strain with a 50% inhibitory concentration (IC 50 ) of 27.7 ؎ 0.5 M, was shown to cause a transformation of the human erythrocyte shape toward that of stomatocytes. Good correlation between the IC 50 value and the membrane curvature changes caused by lupeol was observed. Preincubation of erythrocytes with lupeol, followed by extensive washing, made the cells unsuitable for parasite growth, suggesting that the compound incorporates into erythrocyte membrane irreversibly. On the other hand, lupeol-treated parasite culture continued to grow well in untreated erythrocytes. Thus, the antiplasmodial activity of lupeol appears to be indirect, being due to stomatocytic transformation of the host cell membrane and not to toxic effects via action on a drug target within the parasite. A number of amphiphiles that cause stomatocyte formation, but not those causing echinocyte formation, were shown to inhibit growth of the parasites, apparently via a mechanism similar to that of lupeol. Since antiplasmodial agents that inhibit parasite growth through erythrocyte membrane modifications must be regarded as unsuitable as leads for development of new antimalarial drugs, care must be exercised in the interpretation of results of screening of plant extracts and natural product libraries by an in vitro Plasmodium toxicity assay.

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Section: Discussionmentioning

confidence: 99%

In Vitro Plasmodium falciparum Drug Sensitivity Assay: Inhibition of Parasite Growth by Incorporation of Stomatocytogenic Amphiphiles into the Erythrocyte Membrane

Ziegler

Christensen

Hviid

et al. 2002

Antimicrob Agents Chemother

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“…This can be understood if one considers that upon contact the surfactant molecules immediately insert themselves into the erythrocyte lipid bilayer [53,54], likely increasing its permeability or even its lateral expansion ability, and hence initially conferring hypotonic protection. Ultimately, however, they induce hemolysis due to bilayer solubilisation [17,51,[55][56][57] and formation of mixed micelles. Bilayer solubilisation seems to be more efficient if the added surfactants and the bilayer lipids have similar hydrocarbon chain lengths [22].…”

Section: Hemolytic Activitymentioning

confidence: 99%

Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles

Brito

Marques

Silva

et al. 2009

Colloids and Surfaces B: Biointerfaces

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a b s t r a c tThe design of efficient liposomal systems for drug delivery is of considerable biomedical interest. In this context, vesicles prepared from cationic/anionic surfactants may offer several advantages, mainly due to their spontaneity in formation and long-term stability. There is also an impending need to produce less toxic, more biocompatible amphiphiles, while maintaining the desirable aggregation properties. In this work, we present data for acute toxicity to Daphnia magna (IC 50 ), and potential ocular irritation (HC 50 ) for some newly prepared ionic surfactants with dodecyl chains, derived from the amino acids tyrosine (Tyr), serine (Ser), hydroxyproline (Hyp) and lysine (Lys). The micellization behavior of the compounds, evaluated from surface tension measurements, is presented and compared to more conventional ionic amphiphiles. Two types of spontaneouly formed catanionic vesicles, composed either by a dodecyltrimethylammonium bromide (DTAB)/Lys-derivative and or Ser-/Lys-derivative mixture, have also been tested for their ecotoxicity and hemolytic potential. All the micelle-forming surfactants as well as the vesicle-containing mixtures are found to have lower ecotoxicity than the reference surfactant DTAB. Moreover, the results from hemolysis and hemoglobin denaturation tests show that the Tyr-and Lys-derivatives are moderately irritant, whereas the Hyp-and Ser-ones are just slightly irritant. Even more significantly, the vesicle-containing mixtures exhibit lower hemolytic activity than the neat surfactants, a positive result for their potential use in liposomal formulations.

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“…These agents are often active against a broad range of bacteria and other cells and can also inactive certain viruses (16,29). Because of their high affinity for biological membranes, these agents show a low selectivity and can be damaging to a variety of mammalian cells (17,23,24).Since the time needed to kill microorganisms with cationic surfactants is usually short, it could be expected that side effects in the host might be decreased by the use of substances that are subject to hydrolytic degradation. However, the lifetime of the compounds must be sufficiently long to allow proper inactivation of the undesired microorganisms.…”

mentioning

confidence: 99%

Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components

Lindstedt

Allenmark

Thompson

et al. 1990

Antimicrob Agents Chemother

116

100

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A series of quaternary ammonium compounds that are esters of betaine and fatty alcohols with hydrocarbon chain lengths of 10 to 18 carbon atoms were tested with respect to antimicrobial activities and rates of hydrolysis. When the tetradecyl derivative was tested against some selected microorganisms, the killing effect was comparable to that of the stable quaternary ammonium compound cetyltrimethylammonium bromide. At higher pH values, both the antimicrobial effect and the rate of hydrolysis of the esters increased. However, whereas at pH 6 greater than 99.99% killing of Salmonella typhimurium was achieved with 5 ,ug/ml in 3 min, the rate of hydrolysis was less than 20% in 18 h. At pH 7, a similar killing effect was achieved in 2 min and 50% hydrolysis occurred in ca. 5 h. Thus, it is possible to exploit the rapid microbicidal effect of the compounds before they hydrolyze. The rate of hydrolysis was reduced by the presence of salt. The bactericidal effect of the betaine esters increased with the length of the hydrocarbon chain of the fatty alcohol moiety up to 18 carbon atoms. Since the hydrolysis products are normal human metabolites, the hydrolysis property may extend the use of these quaternary ammonium compounds as disinfectants and antiseptics for food and body surfaces.The membrane-disruptive and antimicrobial activities of cationic surfactants are well recognized. These agents are often active against a broad range of bacteria and other cells and can also inactive certain viruses (16,29). Because of their high affinity for biological membranes, these agents show a low selectivity and can be damaging to a variety of mammalian cells (17,23,24).Since the time needed to kill microorganisms with cationic surfactants is usually short, it could be expected that side effects in the host might be decreased by the use of substances that are subject to hydrolytic degradation. However, the lifetime of the compounds must be sufficiently long to allow proper inactivation of the undesired microorganisms. The products obtained in the degradation steps should also be significantly less toxic than the original compound and should ideally constitute normal metabolites of the host.To explore the possible use of degradable cationic surfactants, we studied a series of amphiphilic betaine esters (Fig. 1). Although the increased rate of base-catalyzed hydrolysis of lower esters of this structure has been investigated and is understood to be caused by an inductive effect from the positive charge (5, 26), this property does not seem to have been considered in connection with biological (10,27) or recent surface chemical (4, 25) studies of compounds of this type. In the present paper, we describe the synthesis of some esters between betaine (trimethylglycine) and long-chain fatty alcohols, their antimicrobial activities, and their rates of hydrolysis. MATERIALS AND METHODSCompounds investigated. The betaine esters were obtained as chlorides by chloroacetylation of the corresponding longchain alcohol, principally as described by Ho...

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Permeability alterations and antihaemolysis induced by amphiphiles in human erythrocytes

Cited by 110 publications

References 50 publications

In Vitro Plasmodium falciparum Drug Sensitivity Assay: Inhibition of Parasite Growth by Incorporation of Stomatocytogenic Amphiphiles into the Erythrocyte Membrane

In Vitro Plasmodium falciparum Drug Sensitivity Assay: Inhibition of Parasite Growth by Incorporation of Stomatocytogenic Amphiphiles into the Erythrocyte Membrane

Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles

Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components

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