Isosteric ribavirin analogues: Synthesis and antiviral activities.

The novel isosteric ribavirin analogues were synthesized by two different ways. Some of them showed significant antiviral action against hepatitis C virus (HCV), herpes simplex (HCV-1) and influenza A virus comparable to that of ribavirin itself. The data obtained confirm the proposed theory of the ribavirin possible antiviral activity mechanism related with bioisosterism.

Distribution coefficient of rifabutin in liposome/water system as measured by different methods.

Distribution coefficient (D) of rifabutin in liposome/water system was measured by phase separation and fluorescence probe quenching techniques. D values were identical suggesting that rifabutin is fully immersed into lipid bilayer. Structural studies of phospholipid bilayer employing (31)P NMR spectroscopy demonstrated that introduction of rifabutin does not alter the bilayer structure. A scheme of the rifabutin position in lipid bilayer based on the calculated size of rifabutin molecule is proposed.

Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates.

Since undesirable activation of the complement system through the classical pathway is associated with tissue damage and other pathologic proinflammatory consequences at ischemia/reperfusion injury, autoimmune diseases, and rejection of allo- and xenografts, creation of selective inhibitors of the classical pathway leaving the alternative pathway intact is of great importance. Classical pathway is triggered by binding of its recognizing unit, protein C1q, to a number of targets like antibodies, pentraxins, apoptotic cells, and others. In order to obtain inhibitors blocking the first step of the classical cascade, synthesis of sulfates of steroids (Delta(5)-3beta-hydroxycholenic, Delta(5)-3beta-hydroxyetiocholenic, deoxycholic, and cholic acids) and triterpenoids (betulin, 20,29-dihydro-20,29-dichloromethylenbetulin, betulinic, ursolic, and oleanolic acids) has been performed. Testing of the compounds in classical pathway inhibition assay has displayed derivatives of triterpenoid betulin (betulin disulfate and betulinic acid sulfate) to be the most potent inhibitors. Further studies of the two compounds established that their activity to inhibit the classical pathway had been due to their capability to block the interaction of C1q with antibodies. Betulin disulfate and betulinic acid sulfate have shown weak inhibition of the alternative route of activation, what makes them promising inhibitors for the selective suppression of the classical complement pathway at the earliest possible level as well as perspective agents for blocking the interaction of C1q with its other targets.

Methylophilus quaylei sp. nov., a new aerobic obligately methylotrophic bacterium.

A new obligately methylotrophic bacterium (strain MTT) with the ribulose monophosphate pathway of carbon assimilation is described. The isolate, utilizing only methanol, is an aerobic, Gram-negative, asporogenous, non-motile short rod multiplying by binary fission. Its cellular fatty acids profile consists primarily of straight-chain saturated C16:0 and unsaturated C16:l acids. The major ubiquinone is Q-8. The dominant phospholipids are phosphatidylethanolamine and phosphatidylglycerol. Diphosphatidylglycerol (cardiolipin) is absent. Optimal growth conditions are 25-29 degree C, pH 6.5 - 7.5, 0.5% CH3OH and 0.05% NaCl. Strain MTT lacks alpha-ketoglutarate dehydrogenase, the glyoxylate shunt enzymes, and glutamate dehydrogenase. Ammonium is assimilated by the operation of the glutamate cycle enzymes: glutamine synthetase and glutamate synthase. An exopolysaccharide consisting of rhamnose, glucose and galactose is formed under nitrogen limitation. The G + C content of the DNA is 54.0 mol%. Based on 16S rDNA sequence analysis and DNA-DNA relatedness (29-34%) with type strains of the genus Methylophilus, the novel isolate was classified as a new species of this genus and named Methylophilus quaylei MTT (VKM B-2338T, DSMZ, etc.).