Gábor Pintér

Diazo Transfer−Click Reaction Route to New, Lipophilic Teicoplanin and Ristocetin Aglycon Derivatives with High Antibacterial and Anti-influenza Virus Activity: An Aggregation and Receptor Binding Study

Semisynthetic, lipophilic ristocetin and teicoplanin derivatives were prepared starting from ristocetin aglycon and teicoplanin psi-aglycon (N-acetyl-D-glucosaminyl aglycoteicoplanin). The terminal amino functions of the aglycons were converted into azido form by triflic azide. Copper catalyzed 1,3-dipolar cycloaddition reaction with lipophilic alkynes resulted in the title compounds. Two of the teicoplanin derivatives showed very good MIC and MBC values against various Gram-positive bacteria, including vanA enterococci. The aggregation and interaction of a n-decyl derivative with bacterial cell wall components was studied. One of the lipophilic ristocetin derivatives displayed favorable anti-influenza virus activity.

Time-lapse analysis of cell death in mammalian and fungal cells.

Time-lapse video microscopy was designed to follow the movement of single cells for an unlimited period of time under physiological conditions. The system is based on two inverted microscopes located in a CO(2) incubator and equipped with charge-coupled device cameras connected to the computer. Frames were recorded every minute and the subsequent video sequence was converted to database form. The system was applied to describe the movements of normal HaCaT cells and Pb-treated cells causing the so-called apoptotic dance during cell death. The apoptotic movement was also followed in high-osmolarity glycerol-type mitogen-activated protein kinase (MAPK) null mutant of Fusarium proliferatum, a filamentous fungus, during osmotic stress. The shortest (20 min) and most vigorous death movements were observed in apoptotic fungal cells subjected to salt stress. The necrotic process at higher Pb concentration (50 microM) took 2-3 h, whereas the apoptotic process at lower Pb concentrations lasted from minutes to days.

Click reaction synthesis of carbohydrate derivatives from ristocetin aglycon with antibacterial and antiviral activity

New sugar derivatives of ristocetin were prepared by copper-catalyzed 1,3-dipolar cycloaddition reaction using azido-ristocetin aglycon and various propargyl glycosides. Some of them were found to be active against gram-positive bacteria and showed favorable antiviral activity against the H1N1 subtype of influenza A virus.

N-glycosylthioureido aglyco-ristocetins without platelet aggregation activity

The water-soluble N-methoxy-PEG-yl-, N-β-D-glucopyranosyl- and N-β-D-maltosylthioureido aglyco-ristocetin were prepared which, in contrast to ristocetin A, did not induce thrombocyte aggregation. The antibacterial activity of N-β-D-maltosylthioureido aglyco-ristocetin A against MRSA was comparable to that of ristocetin A, while its activity against Enterococcus faecalis (VRE, TSE) is somewhat stronger when compared to those of vancomycin and ristocetin A.

Synthesis and antimicrobial activity of ciprofloxacin and norfloxacin permanently bonded to polyethylene glycol by a thiourea linker.

Synthesis and antimicrobial activity of ciprofloxacin and norfloxacin permanently bonded to polyethylene glycol by a thiourea linker

In Situ Electron Microscopy of Lactomicroselenium Particles in Probiotic Bacteria.

Electron microscopy was used to test whether or not (a) in statu nascendi synthesized, and in situ measured, nanoparticle size does not differ significantly from the size of nanoparticles after their purification; and (b) the generation of selenium is detrimental to the bacterial strains that produce them. Elemental nano-sized selenium produced by probiotic latic acid bacteria was used as a lactomicroselenium (lactomicroSel) inhibitor of cell growth in the presence of lactomicroSel, and was followed by time-lapse microscopy. The size of lactomicroSel produced by probiotic bacteria was measured in situ and after isolation and purification. For these measurements the TESLA BS 540 transmission electron microscope was converted from analog (aTEM) to digital processing (dTEM), and further to remote-access internet electron microscopy (iTEM). Lactobacillus acidophilus produced fewer, but larger, lactomicroSel nanoparticles (200–350 nm) than Lactobacillus casei (L. casei), which generated many, smaller lactomicroSel particles (85–200 nm) and grains as a cloudy, less electrodense material. Streptococcus thermophilus cells generated selenoparticles (60–280 nm) in a suicidic manner. The size determined in situ in lactic acid bacteria was significantly lower than those measured by scanning electron microscopy after the isolation of lactomicroSel particles obtained from lactobacilli (100–500 nm), but higher relative to those isolated from Streptococcus thermopilus (50–100 nm). These differences indicate that smaller lactomicroSel particles could be more toxic to the producing bacteria themselves and discrepancies in size could have implications with respect to the applications of selenium nanoparticles as prebiotics.