Sterically hindered phenolic derivatives: effect on the production of Pseudomonas aeruginosa virulence factors, high-throughput virtual screening and ADME properties prediction.

Inhibition of quorum sensing is considered to be an effective strategy of control and treatment of a wide range of acute and persistent infections. Pseudomonas aeruginosa is an opportunistic bacterium with a high adaptation potential that contributes to healthcare-associated infections. In the present study, the effects of the synthesized hybrid structures bearing sterically hindered phenolic and heterocyclic moieties in a single scaffold on the production of virulence factors by P.

Differential induction of C6 glioma apoptosis and autophagy by 3β-hydroxysteroid-indolamine conjugates.

In a previous work, we reported the synthesis of four novel indole steroids and their effect on rat C6 glioma proliferation in vitro. The steroid derived from dehydroepiandrosterone and tryptamine (IS-1) was the most active (52 % inhibition at 10 µM), followed by one of the epimers derived from pregnenolone and tryptamine (IS-3, 36 % inhibition at 10 µM). By contrast, the steroid derived from estrone and tryptamine (IS-2) showed negligible activity at 10 µM.

A Hydrophobic Derivative of Ciprofloxacin as a New Photoinitiator of Two-Photon Polymerization: Synthesis and Usage for the Formation of Biocompatible Polylactide-Based 3D Scaffolds.

A hydrophobic derivative of ciprofloxacin, hexanoylated ciprofloxacin (CPF-hex), has been used as a photoinitiator (PI) for two-photon polymerization (2PP) for the first time. We present, here, the synthesis of CPF-hex and its application for 2PP of methacrylate-terminated star-shaped poly (D,L-lactide), as well a systematic study on the optical, physicochemical and mechanical properties of the photocurable resin and prepared three-dimensional scaffolds. CPF-hex exhibited good solubility in the photocurable resin, high absorption at the two-photon wavelength and a low fluorescence quantum yield = 0.

New 3β-hydroxysteroid-indolamine conjugates: Design, synthesis and inhibition of C6 glioma cell proliferation.

Four novel indole steroids based on dehydroepiandrosterone (IS-1), estrone (IS-2) and pregnenolone (IS-3) were obtained and studied for their ability to inhibit C6 glioma proliferation. A reduction in cell proliferation by 52 ± 13% was observed for IS-1 at 10 μM, whereas IS-3 and abiraterone acetate at 10 μM caused a 36 ± 8% decrease. Surprisingly, the cellular effects reported for abiraterone, namely, cytochrome P450 CYP17A1 inhibition and endoplasmic reticulum stress were not detected for IS-1.

New 20-hydroxycholesterol-like compounds with fluorescent NBD or alkyne labels: Synthesis, in silico interactions with proteins and uptake by yeast cells.

20-hydroxycholesterol is a signaling oxysterol with immunomodulating functions and, thus, structural analogues with reporter capabilities could be useful for studying and modulating the cellular processes concerned. We have synthesized three new 20-hydroxycholesterol-like pregn-5-en-3β-ol derivatives with fluorescent 7-nitrobenzofurazan (NBD) or Raman-sensitive alkyne labels in their side-chains. In silico computations demonstrated the compounds possess good membrane permeability and can bind within active sites of known 20-hydroxycholesterol targets (e.

Effect of the NBD-group position on interaction of fluorescently-labeled cholesterol analogues with human steroidogenic acute regulatory protein STARD1.

Steroidogenic acute regulatory protein (StAR, STARD1) is a key factor of intracellular cholesterol transfer to mitochondria, necessary for adrenal and gonadal steroidogenesis, and is an archetypal member of the START protein family. Despite the common overall structural fold, START members differ in their binding selectivity toward various lipid ligands, but the lack of direct structural information hinders complete understanding of the binding process and cholesterol orientation in the STARD1 complex in particular. Cholesterol binding has been widely studied by commercially available fluorescent steroids, but the effect of the fluorescent group position on binding remained underexplored.

Uptake and metabolism of fluorescent steroids by mycobacterial cells.

Fluorescent steroids BODIPY-cholesterol (BPCh) and 7-nitrobenzoxadiazole-4-amino-(NBD)-labeled 22-NBD-chelesterol (22NC) as well as synthesized 20-(NBD)-pregn-5-en-3β-ol (20NP) were found to undergo bioconversions by Mycobacterium tuberculosis HRv and M. smegmatis mc 155. The major fluorescent products were determined to be 4-en-3-one derivatives of the compounds.

Effect of in vivo and in vitro exposure to electrostatic field on some hematological parameters in rats.

The aim of this study was to investigate the effect of the external electrostatic field (ESF) on some hematological parameters in rats. Both in vivo and in vitro experiments were carried out. In in vivo investigations, rats were exposed to ESF (200 kV/m) during short (1 h) and long periods (6 days, 6 h daily).

Evaluation of the fluorescent probes Nile Red and 25-NBD-cholesterol as substrates for steroid-converting oxidoreductases using pure enzymes and microorganisms.

The fluorescent probes Nile Red (nonsteroidal dye) and 25-{N-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-methyl]amino}-27-norcholesterol (25-NBD-cholesterol) (a cholesterol analog) were evaluated as novel substrates for steroid-converting oxidoreductases. Docking simulations with autodock showed that Nile Red fits well into the substrate-binding site of cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) (binding energy value of -8.3 kcal·mol⁻¹).

22-NBD-cholesterol as a novel fluorescent substrate for cholesterol-converting oxidoreductases.

Docking simulations and experimental data indicate that 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (22-NBD-cholesterol), a common fluorescent sterol analog, binds into active sites of bovine cytochrome P450scc and microbial cholesterol dehydrogenases (CHDHs) and then undergoes regiospecific oxidations by these enzymes. The P450scc-dependent system was established to realize N-dealkylation activity toward 22-NBD-cholesterol, resulting in 7-nitrobenz[c][1,2,5]oxadiazole-4-amine (NBD-NH(2)) formation as a dominant fluorescent product. Basing on LC-MS data of the probes derivatized with hydroxylamine or cholesterol oxidase, both pregnenolone and 20-formyl-pregn-5-en-3β-ol were deduced to be steroidal co-products of NBD-NH(2), indicating intricate character of the reaction.

Effects of low frequency ultrasound on some properties of fibrinogen and its plasminolysis.

Background: Pharmacological thrombolysis with streptokinase, urokinase or tissue activator of plasminogen (t-PA), and mechanical interventions are frequently used in the treatment of both arterial and venous thrombotic diseases. It has been previously reported that application of ultrasound as an adjunct to thrombolytic therapy offers unique potential to improve effectiveness. However, little is known about effects of the ultrasound on proteins of blood coagulation and fibrinolysis.

Formation and functioning of fused cholesterol side-chain cleavage enzymes.

We studied the properties of various fused combinations of the components of the mitochondrial cholesterol side-chain cleavage system including cytochrome P450scc, adrenodoxin (Adx), and adrenodoxin reductase (AdR). When recombinant DNAs encoding these constructs were expressed in Escherichia coli, both cholesterol side-chain cleavage activity and sensitivity to intracellular proteolysis of the three-component fusions depended on the species of origin and the arrangement of the constituents. To understand the assembly of the catalytic domains in the fused molecules, we analyzed the catalytic properties of three two-component fusions: P450scc-Adx, Adx-P450scc, and AdR-Adx.