Synthesis of proteophosphoglycans of Leishmania major and Leishmania mexicana

A novel approach for the synthesis of various fragments of proteophosphoglycans from Leishmania major and Leishmania mexicana proteophosphoglycans has been developed. These compounds have been obtained by coupling alpha-mannosyl and alpha-N-acetyl-glucosamine phosphoramidite derivatives with the serine hydroxyl of various amino acids and peptides to give, after oxidation with tert-BuOOH, phosphotriesters exclusively as alpha-anomers in good yield. The resulting compounds could be deblocked using conventional methods. Glycophosphorylation of preassembled and properly protected peptides was found to be more efficient for the preparation of proteophosphoglycan fragments than a building block approach strategy using a phosphoglycosylserine derivative.     

Synthetic fragments of antigenic lipophosphoglycans from Leishmania major and Leishmania mexicana and their use for characterisation of the Leishmania elongating alpha-D-mannopyranosylphosphate transferase

The phosphorylated branched heptasaccharides 7 and 8, the octasaccharide 9 and the phosphorylated trisaccharides 5 and 6, which are fragments of the phosphoglycan portion of the surface lipophosphoglycans from Leishmania mexicana (5) or L. major (6-9), were synthesised by using the glycosyl hydrogenphosphonate method for the preparation of phosphodiester bridges. The compounds were tested as acceptor substrates/putative inhibitors for the Leishmania elongating alpha-D-mannosylphosphate transferase.     

Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC₅₀ values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC₅₀ values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.     

Spectroscopic and theoretical study of the o-vanillin hydrazone of the mycobactericidal drug isoniazid

A complete and detailed study of the hydrazone obtained from condensation of antituberculous isoniazid (hydrazide of the isonicotinic acid, INH) and o-vanillin (2-hydroxy-3-methoxybenzaldehyde, o-HVa) is performed. It includes structural and spectroscopic analyses, comparing experimental and theoretical results. The compound was obtained as a chloride of the pyridinic salt (INHOVA⁺Cl^?) but it will be referred as INHOVA for the sake of simplicity. The conformational space was searched and optimized geometries were determined both in gas phase and including solvent effects. Vibrational (IR and Raman), electronic and NMR spectra were registered and assigned with the help of computational methods based on the Density Functional Theory. Isoniazid hydrazones are good candidates for therapeutic agents against tuberculosis with conserved efficiency and lower toxicity and resistance than parent INH.     

Vaccination of mice against Leishmania mexicana amazonensis with microsomal fraction associated with BCG

Attempts to develop a satisfactory vaccine against New World cutaneous leishmaniasis have been made with varying success. We found that in mice, pretreated subcutaneously with 2×10⁶ BCG organisms 2 weeks prior to immunization at the same site with as low as 10 μg of a microsomal preparation (Pol-F) of Leishmania mexicana amazonensis, a profound alteration was observed in the course of infection produced by inoculation of virulent amastigotes of the same strain. The BCG-Pol-F vaccine preparation was consistently shown to have a protective capacity associated with larger classical cellular immune response (skin test) and higher specific antibody titres in response to leishmanial challenge dose (1 × 10⁶ amastigotes/mouse).     

Spectroscopic study and antioxidant activity of the inclusion complexes of cyclodextrins and amlodipine besylate drug

The aim of the study was to synthesize and characterization the inclusion complexes of amlodipine besylate (AML) drug with β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) which has antioxidating activity property. The guest/host interaction of AML with β-CD and γ-CD in order to complexation drug in β-CD and γ-CD were investigated. The interaction inclusion complexes was characterized by fourier transform infrared and ultraviolet–visible spectroscopies. The formation constant was calculated by using a modified Benesi–Hildebrand equation at 25 °C. The stoichiometry of inclusion complexes was found to be 1:1 for β-CD and γ-CD with AML drug. The antioxidant activity of AML drug and its inclusion complexes were determined by the scavenging of stable radical 2,2′-diphenyl-1-picrylhydrazyl (DPPH^·). Kinetic studies of DPPH^· with AML and CDs complexes were done. The experimental results confirmed the forming of AML complexes with CDs also these indicated that the AML/β-CD and AML/γ-CD inclusion complexes was the most reactive than its free form into antioxidant activity.     

Spectroscopic study of the long-range interaction in saturated heterocycles

The IR and UV spectra of stereoisomeric piperidines and decahydroquinolines were studied, and it was shown that the spectral characteristics (intensity of the long-wavelength Bohlman band of the C-H vibrations, the oscillator strength for the long-wavelength electron transition, etc.) depend on the orientation of the substituents attached to the 2- and 4-ring atoms. The problem of the capacity of the capacity of the p electrons of nitrogen for partial delocalization owing to the interaction with the anticoplanar -C-H bonds is discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1081–1086, August, 1971     

Spectroscopic study of Mentha oils

The visible fluorescence and excitation spectra of Mentha oils (Japanese mint oil, peppermint oil and spearmint oil) have been recorded. Different physical constants which are characteristic of the fluorescent molecules have been calculated for all three oils. Results reveal that the same group of organic compounds dominate in the oils of peppermint and spearmint, whereas some different compound is present in Japanese mint oil. It is also found that the fluorescence intensity of these oils is comparable to that of Rhodamine 6G dye in methanol solution. Our studies suggest that Mentha oils may be a useful lasing material in the 450–600 nm wavelength range.     

Combinatorial library of peptidotriazoles: identification of [1,2,3]-triazole inhibitors against a recombinant Leishmania mexicana cysteine protease

A library consisting of about half of 800 000 possible peptidotriazoles on 450 000 beads was prepared by solid-phase peptide synthesis combined with a regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition between a resin-bound alkyne and a protected amino azide. The central [1,2,3]-triazole was flanked on each side by two randomized amino acids introduced in a combinatorial approach. Importantly, the formation of the triazole could be performed quantitatively in a randomized fashion. The library was screened on solid phase for inhibitory effect against a recombinant cysteine protease, Leishmania mexicana CPB2.8DeltaCTE and sorted by a high-throughput instrument, COPAS beadsorter (up to 200 000 beads/h). Forty-eight hits were analyzed by MALDI-TOF MS providing structural information about the protease specificity, and 23 peptidotriazoles were resynthesized and evaluated in solution, with the best inhibitor displaying a K(i) value of 76 nM. A one-pot procedure was used to convert Fmoc-amino azides into their corresponding Boc derivatives. The crucial influence of weak interactions with a spacer used for detection by MALDI-TOF MS on screening results was observed.     

Spectroscopic study of germanium-containing compounds

Conclusions The values of C=0 in the IR spectra and the position of the band from the n ^* electronic transition in the UV spectra of the amides R¹CONR²R³ vary linearly with the inductive effect of the R¹ substituent (for R²=R³=H, Alk). This may indicate the absence of the intramolecular coordination Ge 0, where or. The substituent R¹=Ge(C₂H₅)₂ exhibits electron-acceptor properties besides a +I-effect.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 349–352, February, 1984.     

Spectroscopic study of silver state in CaO

Electron spectra of the oxidized states of silver (Ag²⁺) in CaO have been identified by comparison of ESR and diffuse reflectance electron spectra.

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Ag²⁺ CaO .

     

Spectroscopic study of hydrogen bonding in aminoanthrapyridones

By an analysis of the IR spectra of solutions of aminoanthrapyridones in chloroform it was demonstrated that the primary and secondary amino groups in the 1 and 6 positions form an intermolecular hydrogen bond with the CO groups; the amino groups in the 6 position form a stronger hydrogen bond. An anomalous form of the absorption band of the stretching vibrations of the NH group was detected in the IR spectrum of 6-n-hexylamino-3-ethylanthrapyridone. The long-wave band in the electronic spectra of aminoanthrapyridone is related to the band of charge transfer of the unshared pair of electrons of the amino nitrogen atom to the π system of the rings.     

Spectroscopic and structural study of the ambazone hydrochloride

Ambazone, a well-known antimicrobial compound, presents also oncostatic properties. The solid form, obtained by using solvent-drop grinding procedure, was characterized by using several physical techniques such as FTIR, X-ray photoelectron spectroscopy, ¹³C NMR and ¹⁵N NMR spectroscopies, thermal analysis, X-ray powder diffraction and mass spectrometry. Based on these data, it was demonstrated that an ambazone–hydrochloride was obtained: new vibrations corresponding to NH₂ ⁺ were identified. DTA–TG–DSC and MS data revealed that a new crystal type has been obtained. X-ray diffraction data allowed the determination of the lattice parameters and the most probable space group P _21/c was established also with only one molecule per asymmetric unit.     

High-performance liquid chromatographic method for the analysis of a candidate 8-aminoquinoline antileishmanial drug using oxidative electrochemical detection

An analytical method was developed for the quantitation of a candidate antileishmanial drug, 6-methoxy-8-(6-diethylaminohexylamino)-4-methylquinoline, dihydrochloride, in canine plasma. The assay utilized internal standard technique with a structural similar 8-aminoquinoline, 6-methoxy-8-(7-diethylaminoheptylamino)-4-methylquinoline, dihydrochloride, as the internal standard. The method employs a liquid-solid extraction procedure with prepackaged silica gel columns upon which the drug and internal standard are adsorbed, then selectively washed and eluted. Reversed-phase chromatography was then employed to analyze the extracted sample by means of oxidative electrochemical detection at +0.75 V. Good accuracy and precision were obtained over the range of concentration tested (10-1500 ng/ml plasma). Analyses of plasma samples from human volunteers given the drug demonstrate the method is also suitable for analysis of human plasma samples. The entire procedure is relatively simple and requires only 1 ml of plasma.     

Spectroscopic study of calcium sulfite thermolysis

The thermal conversion of calcium sulfite into calcium sulfate in air was studied by thermogravimetric analysis and ESR and IR spectroscopy. The water of crystallization of CaSO₃ · 0.5H₂O was found to be involved in the formation of the heat-generated radical ion SO ₂ ^? . A thermolysis mechanism is suggested.