Polymethyleneamine alkaloids of animal origin. I. Metabolites of marine and microbial organisms

This review, issued in two parts, describes the information on the structure and biological activity of animal alkaloids derived from polymethyleneamines and produced by marine organisms, wasps, spiders, and microorganisms. Animal alkaloids are outstanding models for developing methods and drugs for the treatment of many human diseases. In the first part, we consider compounds produced by marine and microbial organisms. Some promising synthetic analogues of these alkaloids are used in developing modem preparations for the chelate therapy of excessive blood iron content and antituberculosis, antiproliferative, and immunosuppressive drugs. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2005, vol. 31, no. 6; see also http://www.maik.ru.     

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity

A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.     

Dynamics of Pulsed X-Ray Radiation of a Plasma Micropinch Discharge

Plasma Physics Reports - A complex of diagnostic equipment has been created and a measurement procedure has been developed for a multi-channel scintillation X-ray spectrometer with nanosecond time...     

Anti-influenza activity of monoterpene-containing substituted coumarins

Compounds simultaneously carrying the monoterpene and coumarin moieties have been tested for cytotoxicity and inhibition of activity against influenza virus A/California/07/09 (H1N1)pdm09. The structure of substituents in the coumarin framework, as well as the structure and the absolute configuration of the monoterpenoid moiety, are shown to significantly influence the anti-influenza activity and cytotoxicity of the compounds under study. The compounds with a bicyclic pinane framework exhibit the highest selectivity indices (the ratios between the cytotoxicity and the active dose). The derivative of (?)-myrtenol 15c, which is characterized by promising activity, low cytotoxicity, and synthetic accessibility, has the greatest potential among this group of compounds. It exhibited the highest activity when added to the infected cell culture at early stages of viral reproduction.     

Usnic acid derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1

The synthesis of (+)-usnic acid derivatives is described. The derivatives contain one or two cyano groups, connected to the acetophenone fragment of dibenzofuran core by linkers of different length and character, or some other modifications. The influence of these compounds on the activity of recombinant human tyrosyl-DNA phosphodiesterase 1 and MCF-7 tumor cells’ viability has been estimated. The data indicate a distinct dependence of functional characteristics of the compounds on their structure.     

The role of membrane structure in activation of mitochondrial phospholipases. 2. Mechanism of crambin action on the activities of mitochondrial membrane phospholipases and microviscosity

Effects of crambin on the phospholipase activity, lipid peroxidation and structure of mitochondrial membranes have been investigated. Crambin has been shown to inhibit lipid peroxidation and phospholipase activity induced by Ca2+ and freezing-thawing of mitochondria. As shown by ESR studies, these effects are based on the ability of crambin to cause changes in mitochondrial membrane structure.     

Discovery of a New Class of Inhibitors of Vaccinia Virus Based on (−)‐Borneol from Abies sibirica and (+)‐Camphor

A series of the bornyl ester/amide derivatives with N‐containing heterocycles were designed and synthesized as vaccinia virus (VV) inhibitors. Bioassay results showed that among the designed compounds, derivatives 6 , 13 , 14 , 34 , 36 and 37 showed the best inhibitory activity against VV with the IC₅₀ values of 12.9, 17.9, 3.4, 2.5, 12.5 and 7.5 μm , respectively, and good cytotoxicity. The primary structure–activity relationship (SAR) study suggested that the combination of a saturated N‐heterocycle, such as morpholine or 4‐methylpiperidine, and a 1,7,7‐trimethylbicyclo[2.2.1]heptane scaffold was favorable for antiviral activity.     

Anti-viral activity of (−)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009

Influenza is a widespread respiratory infection. Every year it causes epidemics, quickly spreading from country to country, or even pandemics, involving a significant part of the human population of the earth. Being a highly variable infection, influenza easy accumulates the resistance mutations to many antivirals.Usnic acid, a dibenzofuran originally isolated from lichens belongs to the secondary metabolites and has a broad spectrum of biological activity. In humans, it can act as an anti-inflammatory, antimitotic, antineoplasic, antibacterial, and antimycotic agent. In this work we studied for the first time the antiviral activity of usnic acid and its derivatives against the pandemic influenza virus A(H1N1)pdm09. A total of 26 compounds representing (+) and (?) isomers of usnic acid and their derivates were tested for cytotoxicity and anti-viral activity in MDCK cells by microtetrazolium test and virus yield assay, respectively. Based on the results obtained, 50% cytotoxic dose (CTD₅₀) and 50% effective dose (ED₅₀) and selectivity index (SI) were calculated for each compound. Eleven of them were found to have SI higher than 10 (highest value 37.3). Absolute configuration was shown to have critical significance for the anti-viral activity. With minor exceptions, in the pair of enantiomers, (?)-usnic acid was more active comparing to (+)-isomer, but its biological activity was reversed after the usnic acid was chemically modified. Based on the obtained results, derivatives of usnic acid should be considered as prospective compounds for further optimization as anti-influenza substances.     

Synthesis and Hypoglycemic Activity of Aryl(Hetaryl)Propenoic Cyanopyrrolidine Amides

Russian Journal of Bioorganic Chemistry - A series of amides based on (2S)-cyanopyrrolidine and α, β-unsaturated aryl- and hetarylcarboxylic acids have been synthesized. The dependence of...