Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors

Trifluoromethyl-β-amino alcohol 11 [(4S)-tert-butyl 4-amino-6,6,6-trifluoro-5-hydroxyhexanoate] was synthesized in five steps starting from Cbz-l-Glu-OH 5 where the key step involved the introduction of the trifluoromethyl (CF₃) group to oxazolidinone 7, resulting in the formation of silyl ether 8 [(4S,5S)-benzyl 4-(2-(tert-butoxycarbonyl)ethyl)-5-(trifluoromethyl)-5-(trimethylsilyloxy)oxazolidine-3-carboxylate]. Compound 11 was then converted into four tri- and tetra-glutamic acid and glutamine peptides (1-4) possessing a CF₃-ketone group that exhibited inhibitory activity against severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CL^pro).     

A Coculture Based, 3D Bioprinted Ovarian Tumor Model Combining Cancer Cells and Cancer Associated Fibroblasts

Ovarian cancer remains a major public health issue due to its poor prognosis. To develop more effective therapies, it is crucial to set-up reliable models that closely mimic the complexity of the ovarian tumor's microenvironment. 3D bioprinting is currently a promising approach to build heterogenous and reproducible cancer models with controlled shape and architecture. However, this technology is still poorly investigated to model ovarian tumors. In this study, a 3D bioprinted ovarian tumor model combining cancer cells (SKOV-3) and cancer associated fibroblasts (CAFs) are described. The resulting tumor models show their ability to maintain cell viability and proliferation. Cells are observed to self-assemble in heterotypic aggregates. Moreover, CAFs are observed to be recruited and to circle cancer cells reproducing an in vivo process taking place in the tumor microenvironment. Interestingly, this approach also shows its ability to rapidly generate a high number of reproducible tumor models that can be subjected to usual characterizations (cell viability and metabolic activity; histology and immunological studies; and real-time imaging). Therefore, these ovarian tumor models can be an interesting tool for high throughput drug screening applications.     

Zur Wasserdampfdestillation von Ammoniak aus Bodenextrakten

Zusammenfassung Es wird eine rasche und selektive Wasserdampfdestillation von Ammoniak aus Bodenextrakten beschrieben. Um eine Störung der Titration durch Kohlensäure zu vermeiden, wird Strontiumchlorid zum Extrakt im Destillierkolben hinzugefügt. Die Destillation erfolgt bei pH 8 in boratgepufferter Lösung.     

Effect Of Propene, <Emphasis Type="Italic">n</Emphasis>-Decane,and Toluene Plasma Kinetics on NO Conversion in Homogeneous Oxygen-Rich Dry Mixtures at Ambient Temperature

A photo-triggered discharge is used to study the influence of three hydrocarbons (HCs), propene (C₃H₆), n-decane (C₁₀H₂₂), and toluene (C₆H₅CH₃) on NO conversion in N₂/O₂/NO/HC mixtures, with 18.5% O₂ concentration, 700 ppm of NO, and an hydrocarbon concentration ranging between 190 ppm and 2,700 ppm. The electrical system generates a transient homogeneous plasma, working under 400 mbar total pressure, with a 50 ns short current pulse at a repetition frequency up to a few Hz. The NO concentration at the exit of the reactor is quantified using absolute FTIR spectroscopy measurements, as a function of the specific deposited energy in the discharge and the mixture composition. Owing to the plasma homogeneity, the experimental results can be compared to predictions of a self-consistent 0-D discharge and kinetic model based on available data in the literature about reactions and their rate constants. It is shown that the addition of either propene (as for DBD or corona discharges) or n-decane to N₂/O₂/NO leads to an improvement of the NO removal as compared to the mixture without hydrocarbon molecules. The adopted kinetic schemes explain this effect for the two mixture types. On the other hand, both the experiments and model predictions emphasize that the addition of toluene does not lead to the improvement of NO conversion. Moreover, compounds that are useful for NO _x reduction catalysis, such as aldehydes, are less produced in the mixture with toluene.     

Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioisomers for Antimalarial,Antiproliferative and Antimicrobial Activities

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC₅₀ = 24 nM) than Puromycin (IC₅₀ = 270 nM) and Doxorubicin (IC₅₀ = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).     

Reductive monoalkylation of nitro aryls in one-pot

The scope of the serendipitous reductive monoalkylation of ethyl (4-methoxy-3-nitrophenyl) acetate taking place during reduction of the nitro functionality to the corresponding primary amine when treated with hydrogen (1 atm) over Pd/C (10%) in ethanol is investigated. Upon prolonged reaction time the reaction conducted in ethanol and methanol yields significant amount of the corresponding secondary amines, while when performed in n-butanol and i-propanol it only resulted in the formation of a small amount of the corresponding secondary amines. Further development of the reductive monoalkylation reaction provided conditions that facilitate conversion of a range of different nitro aryls in one-pot to the corresponding secondary benzyl amino aryls in mostly good to excellent yields. This is accomplished by using hydrogen (1 atm) over Pd/C (10%) as reducing agent and benzaldehyde as the benzyl source combined with a stepwise reaction sequence. This chemistry was further extended to the formation of substituted benzyl amino aryls. The yields of the latter products varied dramatically depending on the substitution patterns associated with the benzaldehyde. However, by altering the reaction conditions it was possible to improve the yields of the benzylated products.     

Adsorption of Polycation and Anionic Surfactant onto Iron Surfaces and the Inhibition of Carbon Dioxide Corrosion

The adsorption process of two polycations (pDADMAC and C‐PAM) with different charge densities has been investigated using the quartz crystal microbalance technique with dissipation monitoring (QCM‐D). The effect of the charge density of the polycation, the NaCl concentration, and the complexation with an anionic surfactant are addressed in this work. X‐ray photoelectron spectroscopy and atomic force microscopy were utilized to analyze the adsorbate with respect to the film coverage and film structure. The corrosion‐inhibiting performance of the films on high‐purity iron in a CO₂ saturated brine, at 25°C, 1 bar CO₂, and pH 4, was investigated by the linear polarization resistance technique. It was found that the polycations adsorbed onto the iron surface, but the corrosion rate of 1 mm yr^?1 was not lowered. However, the polycations formed a complex with an anionic surfactant, and such films showed excellent inhibition performance. Both films, of pDADMAC/SDS and of C‐PAM/SDS, lowered the corrosion rate of iron below 0.01 mm yr^?1. The SDS concentration was below the cmc. It is believed that the SDS adsorbed into the preadsorbed polycation film, forming a complex structure resulting in a hydrophobic and dense film.     

pH-dependent modification of lipophilicity of porphyrin-type photosensitizers

Structural modifications of photosensitizers (changes in protonation, ionic state and aggregation state) under different environmental conditions should be precisely determined to understand the interaction of the photosensitizers with biological systems. In the present study partition coefficients of hematoporphyrin IX (HpIX), disulfonated meso-tetraphenylporphine, meso-tetra(3-hydroxyphenyl)porphine (mTHPP) and meso-tetra(3-hydroxyphenyl)chlorin in the 1-octanol-phosphate buffer system were determined in the pH region 4.0-8.0. Only the partition coefficients of HpIX and mTHPP were found to be pH dependent. Computer processing of fluorimetric titration data was applied to estimate pKa values of the imino nitrogens of mTHPP. Monoprotonated species of mTHPP seem to be unstable or nonexistent. The possibility that both imino nitrogens of this dye are protonated according to a common pKa is proposed. The pKa value of the imino nitrogens of mTHPP was found to be 2.99 +/- 0.04 after the application of a model taking aggregation of the drug into account. The contributions of various aqueous ionic species of mTHPP as functions of pH were calculated and compared with partition coefficients.     

Magnetic and spectroscopic properties of copper(II) complexes with 1-salicoyl-4-phenylthiosemicarbazide

Summary Cu^II complexes of 1-salicoyl-4-phenylthiosemicarbazide (SPT) have been synthesized and characterized by means of elemental analysis, magnetic measurements, and i.r. and e.p.r. spectroscopic methods; ¹H- and ¹³C-n.m.r. and mass spectral data on the thiosemicarbazide are also reported. A paramagnetic complex _eff= 1.298 B.M., is formed with copper(II) sulphate; the low magnetic moment and the e.p.r. spectral data suggest a binuclear species. A diamagnetic complex due to a strong Cu-Cu interaction has been isolated with copper(II) chloride.