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•Dicephalic chlorides show strong antifungal activity against planktonic and biofilm forms.•Dicephalic surfactants inhibit Candida albicans filamentation.•Dicephalic surfactants ...reduce C. albicans adhesion to stainless steel.•Dicephalic surfactants induce ROS production and lipid droplet accumulation in C. albicans.
The studies were aimed to contribute to the elucidation of the relationships between structure of the double-headed cationic surfactants – N,N-bis3,3′-(dimethylamine)propylalkylamide dihydrochlorides and N,N-bis3,3′-(trimethylammonio)propylalkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31), which are of particular interest, as they contain a labile amide group in the molecule and their antifungal activity. Therefore, the minimal inhibitory and fungicidal concentrations (MIC and MFC) of dicephalic surfactants against various fungi were tested using standardized methods. Most of the tested fungi were resistant to the Cn(TAPABr)2 compounds. The strongest growth inhibition was caused by Cn(DAPACl)2 series, which MICs ranged from 6.5 to 16 μM. The influence of dicephalic surfactants on Candida albicans biofilm and adhesion to the various surfaces was investigated with crystal violet staining or colony counting. The reduction of fungal adhesion was also observed, especially to the glass surface. One of the compounds (C14(DAPACl)2) caused DNA leakage from C. albicans cells. Further studies showed the impact of dicephalic surfactants on ROS production, accumulation of lipid droplets and filament formation. This study points to the possibility of application of dicephalic surfactants as the surface-coating agents to prevent biofilm formation or as disinfectants. The results give an insight into the possible mechanism of action of newly synthesized dicephalic surfactants in yeast cells.
A generic activation mode for asymmetric LUMO-lowering catalysis has been developed using the long-established principles of oxy-allyl cation chemistry. Here, the enantioselective conversion of ...racemic α-tosyloxy ketones to optically enriched α-indolic carbonyls has been accomplished using a new amino alcohol catalyst in the presence of electron-rich indole nucleophiles. Kinetic studies reveal that the rate-determining step in this SN1 pathway is the catalyst-mediated α-tosyloxy ketone deprotonation step to form an enantiodiscriminant oxy-allyl cation prior to the stereodefining nucleophilic addition event.
The asymmetric total syntheses of the natural products (+)- and (−)-frondosin B and (+)-frondosin A are reported based on a diastereoselective cycloaddition between tetrabromocyclopropene and an ...annulated furan to provide a highly functionalized common building block. The bridged bicyclic intermediate could be stereo- and chemoselectively manipulated to produce the two structurally distinct members of the frondosins. Both syntheses feature regioselective palladium-coupling reactions and an unprecedented phosphine-mediated ether bridge cleavage. Surprisingly, the planned enantioselective synthesis of frondosin B led to the opposite epimer of the natural product, suggesting an unusual late stage stereoinversion at C8. Frondosin A, but not frondosin B, was shown to have selective antiproliferative activity against several B-cell lines.
Our research aimed to expand the knowledge of relationships between the structure of multifunctional cationic dicephalic surfactants with a labile linker—
N
,
N
...-bis3,3-(dimethylamine)propylalkylamide dihydrochlorides and
N
,
N
-bis3,3-(trimethylammonio)propylalkylamide dibromides (alkyl: n-C
9
H
19
, n-C
11
H
23
, n-C
13
H
27
, n-C
15
H
31
)—and their possible mechanism of action on fungal cells using the model organism
Saccharomyces cerevisiae.
General studies performed on surfactants suggest that in most cases, their main mechanism of action is based on perforation of the cell membranes and cell disruption. Experiments carried out in this work with cationic dicephalic surfactants seem to modify our understanding of this issue. It was found that the investigated compounds did not cause perforation of the cell membrane and could only interact with it, increasing its permeability. The surfactants tested can probably penetrate inside the cells, causing numerous morphological changes, and contribute to disorders in the lipid metabolism of the cell resulting in the formation of lipid droplet aggregates. This research also showed that the compounds cause severe oxidative stress within the cells studied, including increased production of superoxide anion radicals and mitochondrial oxidative stress. Dicephalic cationic surfactants due to their biodegradability do not accumulate in the environment and in the future may be used as effective antifungal compounds in industry as well as medicine, which will be environmentally friendly.
Key points
• Dicephalic cationic surfactants do not induce disruption of the cell membrane.
• Surfactants could infiltrate into the cells and cause accumulation of lipids.
• Surfactants could cause acute oxidative stress in yeast cells.
• Compounds present multimodal mechanism of action.
Graphical abstract
We perform a detailed comparative study of conventional transverse magneto-optical Kerr effect (T-MOKE) measurements and a methodology that utilizes an effective polarization detection scheme for ...mixed s- and p-polarized incoming light. To test the ultimate sensitivity of both methods, we also design a series of specialized samples in which the T-MOKE signal of a Co-film is artificially reduced by means of a Ag overcoat of varying thickness. We find that the effective polarization detection scheme leads to a more than 30-fold increase of the T-MOKE signal and signal-to-noise ratio, even under general operation conditions which were not individually optimized. This allowed for the observation of T-MOKE hysteresis loops of Co-films that were buried under 80 nm of Ag, for which the MOKE signal was only 1/600 of that for an uncoated Co-film. In comparison, conventional T-MOKE measurements did not succeed for Ag overcoats thicker than 40 nm.
We present a new methodology that enables a significant sensitivity improvement for transverse magneto-optical Kerr effect (T-MOKE) detection. For this purpose, we developed a novel measurement ...scheme, in which the polarization detection conditions are changed during the measurement sequence in a pre-defined way. An analytical expression of the associated T-MOKE signal pattern was derived, which allowed us to analyze and classify our experimental data in a straightforward way. Furthermore, this new measurement approach enables the identification of noise and false background signals that might be generated by the sample under investigation, the environment or the detection system itself and it provides a pathway to unambiguously separate all these effects from true T-MOKE signals. These capabilities significantly increase the sensitivity and robustness of T-MOKE detection. The method enabled us to measure magneto-optical signals for samples that are paramagnetic at room temperature or exhibit really small magneto-optical responses, even in the presence of false signals that were far larger in size. Our new methodology was integrated into a scanning wafer tool, which allows for nondestructive, laterally resolved surface characterization measurements and even has the capability of measuring optical and magneto-optical properties simultaneously.
A catalogue of eclipsing variables Malkov, O. Yu; Oblak, E.; Snegireva, E. A. ...
Astronomy and astrophysics (Berlin),
02/2006, Letnik:
446, Številka:
2
Journal Article
Recenzirano
Odprti dostop
A new catalogue of 6330 eclipsing variable stars is presented. The catalogue was developed from the General Catalogue of Variable Stars (GCVS) and its textual remarks by including recently published ...information about classification of 843 systems and making corresponding corrections of GCVS data. The catalogue1 represents the largest list of eclipsing binaries classified from observations.
Natural products have long been recognized as a rich source of potent therapeutics but further development is often limited by high structural complexity and high molecular weight. In contrast, at ...the core of the thujaplicins is a lead-like tropolone scaffold characterized by relatively low molecular weight, ample sites for diversification, and metal-binding functionality poised for targeting a range of metalloenzyme drug targets. Here, we describe the development of this underutilized scaffold for the discovery of tropolone derivatives that function as isozyme-selective inhibitors of the validated anticancer drug target, histone deacetylase (HDAC). Several monosubstituted tropolones display remarkable levels of selectivity for HDAC2 and potently inhibit the growth of T-cell lymphocyte cell lines. The tropolones represent a new chemotype of isozyme-selective HDAC inhibitors.
Quaternary ammonium salts (QASs) are commonly used in medicine, agriculture and industry and their wide usage caused the development of microbial resistance, thus there is still a need for new ...effective antimicrobial agents. Present work describes the biological activity of alanine‐ (DMALM‐n) and glycine‐derived (DMGM‐n) QASs against planktonic and biofilm forms of micro‐organisms. The antimicrobial activity was dependent mainly on the hydrocarbon chain length and surfactants with 12–16 atoms of carbon in the alkyl chain were the most active ones. The lowest MIC value was determined for DMALM‐14 against Rhodotorula rubra and Saccharomyces cerevisiae (2·5 µmol l−1). Generally, alanine derivatives showed stronger effects against micro‐organisms than glycine‐derived QASs. Alanine‐derived surfactants with 12–16 carbons in the alkyl chain had antiadhesive properties on the polystyrene surface, preventing cell attachment (about 70% of inhibition for C. albicans and 40% for S. epidermidis). Strong adhesion reduction was also observed on the stainless steel surface and the highest reduction was observed for C. albicans cells incubated on surface pretreated with DMGM‐16. Moreover, DMGM‐16 and DMALM‐16 prevented C. albicans filamentation, one of the determinants of cell adhesion. Surfactants with C16 alkyl chain (DMGM‐16 and DMALM‐16) eradicated bacterial and yeast biofilm (from 60 to 90% of reduction observed after incubation of the previously grown biofilm in the presence of the highest tested concentration of the surfactant – 400 µmol l−1) and reduced its viability. Strong antimicrobial activity as well as antiadhesive properties make alanine‐ and glycine‐derived QASs the potential candidates for future application as disinfectants.
Significance and Impact of the Study
Cationic surfactants are used in many fields, among others in medicine, cosmetic and pharmaceutical industry. Their usage on a large scale caused the development of microbial resistance mechanisms to such compounds. Thus, there is a need to synthesize new surfactants with potential application as effective disinfectants to combat both planktonic and biofilm forms of micro‐organisms. Present work focuses on the antimicrobial activity of chosen quaternary ammonium salts.
Significance and Impact of the Study: Cationic surfactants are used in many fields, among others in medicine, cosmetic and pharmaceutical industry. Their usage on a large scale caused the development of microbial resistance mechanisms to such compounds. Thus, there is a need to synthesize new surfactants with potential application as effective disinfectants to combat both planktonic and biofilm forms of micro‐organisms. Present work focuses on the antimicrobial activity of chosen quaternary ammonium salts.
A stereocontrolled approach to a key platensimycin intermediate was achieved from a commercially available furylcarboxylate. Key to our approach is the highly efficient formal 4 + 3 cyclocondensation ...of a substituted furan with tetrabromocyclopropene along with an intramolecular γ-alkylation to construct the final ring of the caged intermediate.
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