Angelica V. Sharapova

Synthesis, biological activity, distribution and membrane permeability of novel spiro-thiazines as potent neuroprotectors

New spiro-derivatives of 1,3-thiazine - potential neuroprotectors have been synthesized. It has been determined that the obtained compounds are biologically active and capable of blocking the glutamate-induced calcium ion uptake into synaptosomes of rat brain cortex. The inhibitory activity of the test substances was shown to depend on the chemical nature and structure of the substituents bound with an exocyclic nitrogen atom. Non-polar alkyl and polar radicals with halogen, oxygen and nitrogen atoms were used as substituents. It is typical of the active spiro-thiazines to have alkyl substituents in ortho- and para-position of the benzene ring. Among the investigated spiro-thiazines it is the derivatives with ethyl- and isopropyl-groups in the aril part of the molecules that are the lead-compounds with a high inhibitory ability. We measured the distribution coefficients of the substances in octanol/buffer and hexane/buffer systems and made conclusions about the ability of the investigated drug-like compounds to penetrate the biological membranes. By using the parabolic model we derived a quadratic equation that allowed us to evaluate quantitatively the inhibitory activity of spiro-thiazines with hydrophobic substituents based on lipophilicity data. We also studied the permeability through the phospholipidic membrane and introduced a correlation equation describing the dependence of the investigated spiro-thiazines activity on the descriptors characterizing the donor-acceptor properties.

Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials.

Aqueous solubility and distribution of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin antimicrobials drugs in octanol/buffer system has been measured by the isothermal saturation method using buffer solutions pH2.0 and 7.4 in the temperature range of 293.15-313.15K. Thermophysical characteristics for the compounds have been determined by the DSC method. It has been established that the solubility of levofloxacin in these buffers is higher than that of the other fluoroquinolones. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor-acceptor capacity of the molecules on drugs solubility has been studied. According to the lipophilicity parameter fluoroquinolones are ranged in the following order: enrofloxacin>levofloxacin>ciprofloxacin>norfloxacin. The thermodynamic solubility and distribution functions of the studied compounds have been obtained. The permeability coefficients of the substances through an artificial phospholipid membrane were determined. The drugs with a lower aqueous solubility were estimated to have higher distribution coefficients and membrane permeability.

On the Nature of Interaction Between Fullerene and Aniline

Abstract Interaction between fullerene C60 and N,N‐dialkyl‐substituted anilines was studied by gas–liquid chromatography (GLC) and titration calorimetry. The GLC study was performed at 140–200°C in the poly(tetramethylbenzene) solvent with ultra‐high solubility of C60. No interaction of the C60–aniline type was registered under such conditions. Calorimetric titration performed at 25°C in a non‐aromatic solvent confirmed the lack of complex formation. Minute exoeffect registered is explained by suppressing of the rotation motion of the C60 molecules accompanied by energy dissipation for the aniline environment.

New derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors: Synthesis, biological testing and solubility in pharmaceutically relevant solvents

The derivatives of hydrogenated pyrido[4,3-b]indoles as potential neuroprotectors have been synthesized. The different substituents were introduced into position 8 of the carboline fragment of the molecule: methyl-, methoxy-, fluorine- and chlorine-. Biological tests have shown that all the studied compounds can modulate glutamate-dependent uptake of calcium ions in rats’ cerebral cortex synaptosomes. The shake-flask method was used to measure the solubility of the compounds in the buffer solution (pH 7.4), hexane and 1-octanol within the temperature interval of 293.15–313.15 К. All the derivatives have been found to have low solubility (not exceeding 8 ∙ 10−4 mole fractions) in the mentioned solvents. The effect of thermophysical and protolytic properties of the compounds on the solubility have been studied and the thermodynamic functions of compounds dissolution in the solvents used have been calculated.

Interactions of copper tetra-tert-butylphthalocyanine with nitrogen- and sulfur-containing compounds in solutions

Interactions of ammonia, aliphatic amines, hydrogen sulfide, and sulfur dioxide with copper tetra-tert-butylphthalocyanine (CuPc) in squalane were studied by spectrophotometry and gas liquid chromatography in the CuPc concentration range of 1·10–3—5·10–2 mol L–1. The sorption properties of the CuPc—squalane stationary liquid phases (SLPs) are governed by the physicochemical nature of the CuPc nanoaggregates in solution. The β-type nanoaggregates exhibit particularly high activity to hydrogen sulfide; the activities to primary and secondary amines are also high.

EFFECT OF 2-HYDROXYPROPYL- β -CYCLODEXTRIN ON SOLUBILITY OF NOVEL CYTOTOXIC COMPOUNDS

Методом УФ-спектроскопии изучены процессы комплексообразования в системах 2-гидроксипропил-β-циклодекстрин − цитотоксические вещества в интервале температур 293-315 К. Доказано образование супрамолекулярных соединений включения стехиометрического состава 1:1. Рассчитаны константы устойчивости комплексов и термодинамические параметры образования соединения включения 2-гидроксипропил-βциклодекстрин − трис(1-пентил-1Н-индол-3-ил)метанол. Установлено, что полученный комплекс 2-гидроксипропил-β-циклодекстрин − хлорид трис(1-пентилиндол-3-ил)метилия является неустойчивым.

Gas-Chromatographic Study of the Polarity and Selectivity of Nematic Liquid Crystals

The sorption properties of stationary phases based on nematic p-substituted azoxybenzenes were studied. Correlations were revealed between the structural selectivity of mesogens, chemical nature of terminal substituents, capability for dispersion interactions and polarity of the sorbents, temperature gradient of the retention indices, and thermodynamic parameters of solution of xylene isomers in the sorbents.