Том 42, № 2 (2016)

Usnic acid (UA) is a commercially available lichen metabolite. Its biological activity is diverse. Its broad occurrence in various lichen species, simple isolation procedure, and high optical purity of the isolated product make it promising as a base for developing novel pharmaceuticals. To date, scientific progress has made it possible to expand the scope of applications of UA and comprehend the biological mechanisms mediating its action. This review of the biological activity of UA and its derivatives summarizes publications of the recent decade. New data on the mechanisms of UA action on living organisms are discussed, and ways to modify its biological activity by altering its chemical structure and to control its bioavailability are considered. Special attention is paid to prospects of using semisynthetic UA derivatives as pharmacological agents. Data on the influence of the enantiopurity of UA on its biological activity are analyzed. The first part of the review is dedicated to UA biosynthesis and the biological action of UA and its derivatives on unicellular organisms.

We describe herein a new method for cleaving from resin and removing acid-labile protecting groups in solid-phase peptide synthesis in the presence of a polyfluorinated alcohol (either trifluoroethanol, TFE, or hexafluoroisopropanol, HFIP). It was shown that 0.1 M HCl in hexafluoroisopropanol or trifluoroethanol removes the acid-labile protecting groups commonly used in Fmoc SPPS for the protection of amino acid side-chains, such as t-butyl ester and ether, Boc, trityl, and Pbf groups including the most acid-resistant p-hydroxymethylphenoxyacetyl group (HMPA), p-benzyloxy benzyl ester (Wang resin), Rink amide, and peptide amide linker (PAL). The addition of 5–10% of a hydrogen-bonding solvent was shown to considerably retard or even fully inhibit the reaction. However, nonhydrogen-bonding solvents, such as dichloromethane, do not slow down the reaction.

Characteristic changes in some parameters of white muscle mitochondria (mitochondrial volume, activity of cytochrome c oxidase (COX, EC 1.9.3.1) and the level of Cox1, Cox2, Cox4, and Cox6 subunit gene expression and activity and kinetic characteristics of mitochondrial lactate dehydrogenase isozymes (mtLDH, EC 1.1.1.27)) in adaptation to seasonal decrease in temperature from 16 to 6°C of one-year juvenile brown trout Salmo trutta L. from rivers of Lake Onega basin were investigated. A 1.5-fold increase in the activity of COX, and the increase in the levels of gene expression of both Cox4 and Cox6 nuclear subunits and increased activity of mitochondrial LDH isozymes, which have a low affinity towards lactate, has been shown. The possible role of nuclear and mitochondrial subunits of cytochrome c oxidase in improving the efficiency of the enzyme in molecule biogenesis and further modulation of its activity, as well as regulation of pyruvate formation to maintain the required rate of oxidative phosphorylation in mitochondria under low temperature were discussed.

Seven fluorescent symmetric dimeric bisbenzimidazoles DB(n) capable of occupying up to one turn of the double-stranded B-form DNA have been designed and synthesized with the aim to develop DNAdependent enzyme inhibitors. The DB(n) compounds contain four 2,6-substituted benzimidazole fragments and differ by the length of the oligomethylene linker (n = 1, 2, 6, 8, 9, 10, 12) between the bisbenzimidazole blocks. The formation of DB(n)–double-stranded DNA complexes and the localization of the ligands in the DNA minor groove have been confirmed by a number of physicochemical methods.

The aim of the research was to investigate the anti-bacterial potential of some N-substituted sulfonamides bearing benzodioxane moiety. The synthesis was started by reaction of N-2,3-dihydrobenzo[1,4]dioxin-6-amine with 4-acetamidobenzene-1-sulfonyl chloride in the presence of 10% aqueous Na₂CO₃ solution to yield N-(2,3-dihydrobenzo[1,4]-dioxin-6-yl)-4-acetamidobenzenesulfonamide, which was further reacted with alkyl/aralkyl halides in DMF and lithium hydride as a base to afford N-substituted-N-(2,3dihydro-[1,4]-benzodioxin-6-yl)-4-acetamidobenzenesulfonamides. All the synthesized compounds were characterized by spectral data (IR, ¹H NMR, EI-MS, and HR-MS). The compounds were tested for antibacterial activity and most of them exhibited potent therapeutic potential against various Gram-negative and Gram-positive strains.

New diamino derivatives of pyrano[3,4-c]pyridines were synthesized by the pyridine ring recyclization. The presence of the intramolecular hydrogen bond in 6-[(4-methoxyphenyl)amino]-3,3-dimethyl8-methylamino-3,4-dihydro-1H-pyrano[3,4-c]pyridin-5-carbonitrile was identified by X-ray diffraction. A pharmacological study of the synthesized compounds was carried out in known tests, such as assay for antagonism induced by corazole subcutaneous injection and the open field test. The method of rotating rod was used to evaluate neurotoxicity. The diamino derivatives of pyrano[3,4-c]pyridines were found to possess neutrotropic properties. The synthesized compounds, as well as diazepam, prevent the occurrence of clonic seizures and clonic corazoleinduced convulsions in animals; however, they cause a behavior-depressing sedative effect.