Membrane-active compounds

Since the usage of PCMC in Europe is getting more difficult due to AOX problems in waste water treatment, despite the fact that the biodegradability of PCMC has been proven (Bayer AG, 1998), our research groups examined whether the chlorine atom in PCMC is necessary or whether a substitution of chlorine is possible. We found that a chlorine substitution by numerous functional groups also led to active ingredients, which were however not as active as PCMC. Also no compound had the well-balanced activity spectrum of PCMC. Therefore it can be concluded that the chlorine function in PCMC is necessary for its activity (Bayer AG, 2001a). 

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Giuliani A, Pirri G, Bozzi A, Di Giulio A, Aschi M, Rinaldi AC (2008) Antimicrobial peptides natural templates for synthetic membrane-active compounds. Cell Mol Life Sci 65 2450-2460... 

Vohnsky R, Kliger M, She3mis T, Kolusheva S, Jehnek R. Glass-supported lipid/polydiacety-lene films for colour sensing of membrane-active compounds. Biosens Bioelectron 2007 22 3247-3251. 

During the last decades several drugs and compounds have been identified that to different degrees are able to overcome MDR so that the cells resemble sensitive cells in their chemosensitivity. These drugs mainly include catamphiphilic, membrane-active compounds and belong to various classes of drugs such as calcium channel blockers (verapamil), neuroleptics (flupentixol), anesthetics, antimalarial drugs (quinidine), antiarrhythmics (amiodarone), and many other compounds. Reviews were recently published [61, 157]. 

Schuller. C.. Mamnun, Y.M., Wolfger, H., Rockwell. N.. Thorner, J., and Kuchler, K. (2007) Membrane-active compounds activate the transcription factors Pdrl and Pdr3 connecting pleiotropic drug resistance and membrane lipid homeostasis in Saccharomyces cerevisiae. Molecular Biology of the Cell, 18, 4932-4944. 

Membrane-active compounds can elicit adverse effects in three primary ways. First, compounds that are positively charged at physiologic pH may alter membrane surface potential in a manner proportional to their concentration in the membrane. This in turn could have an adverse effect on membrane function. Second, the chemical may absorb... 

Polyene antibiotics such as amphotericin, nystatin, or filipin are examples of inainly hydrophobic molecules that also have polar groups. In water, these cyclic molecules tend to aggregate to shield their hydrophobic surfaces from water. These compounds are readily incorporated into natural as well as model membranes and tend to aggregate in the bilayer, now in a reversed manner, i.e. shielding their polar groups from the hydrophobic interior of the membrane. The antibiotics form complexes with sterols and act as membrane active compounds in the sense that the bilayers become leaky [116,117]. 

J. T. F. Keurentjes, F. J. M. Voermans, Membrane separations in the production of optically pure compounds in Chirality and Industry II. Developments in the Manufacture and applications of optically active compounds, A. N. Collins, G. N. Sheldrake, J. Crosby (Eds.), John Wiley Sons, New York (1997) Chapter 8. 

TBT and TFT are membrane-active molecules, and their mechanism of action appears to be strongly dependent on organotin(IV) lipophilicity. They function as ionophores and produce hemolysis, release Ca(II) from sarcoplasmic reticulum, alter phosphatodylseiine-induced histamine release, alter mitochondrial membrane permeability and perturb membrane enzymes. Organotin(IV) compounds have been shown to affect cell signaling they activate protein kinase and increase free arachidonic acid through the activation of phospholipase... 

The intracellular processes which precede membrane activation appear to differ from those of MOE neurones, in that cyclic nucleotide gating may not occur. The transduction process which induces current flow in snake VN neurones, utilises as a putative second-messenger the modulator compound inositol triphosphate — Ins. (1,4,5) P3 = IP3 (Liu et al, 1999 Taniguichi et al, 2000). The proposed channel component associated with the microvillous membrane is one of the transient receptor potential family (TRPC-2 Heading Fig., pp. 94), the p-splice... 

The main classes of plasticizers for polymeric ISEs are defined by now and comprise lipophilic esters and ethers [90], The regular plasticizer content in polymeric membranes is up to 66% and its influence on the membrane properties cannot be neglected. Compatibility with the membrane polymer is an obvious prerequisite, but other plasticizer parameters must be taken into account, with polarity and lipophilicity as the most important ones. The nature of the plasticizer influences sensor selectivity and detection limits, but often the reasons are not straightforward. The specific solvation of ions by the plasticizer may influence the apparent ion-ionophore complex formation constants, as these may vary in different matrices. Ion-pair formation constants also depend on the solvent polarity, but in polymeric membranes such correlations are rather qualitative. Insufficient plasticizer lipophilicity may cause its leaching, which is especially undesired for in-vivo measurements, for microelectrodes and sensors working under flow conditions. Extension of plasticizer alkyl chains in order to enhance lipophilicity is only a partial problem solution, as it may lead to membrane component incompatibility. The concept of plasticizer-free membranes with active compounds, covalently attached to the polymer, has been intensively studied in recent years [91]. 

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