Nikolina Berova

SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A) and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses. The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent.

Assignment of relative and absolute configuration of acyclic polyols and aminopolyols by circular dichroism - trends follow fischer's sugar family tree

Abstract Reference CD curves (measured in methylcyclohexane) of a homologous series of 1 ,2-polyols up to pentols derivatized as anthroates at 1-OH and p-methoxycinnamates at the remaining hydroxyl groups show a systematic trend that greatly simplifies assignments of relative and absolute configurations. The same trend also holds for the corresponding 1-aminopolyols, but not for 2-aminopolvols.

ASSIGNMENT OF ABSOLUTE STEREOCHEMISTRY OF AMINOPOLYOLS BY THE BICHROMOPHORIC EXCITON CHIRALITY METHOD

A general procedure for assigning relative and absolute configurations to multiple stereocentres in acyclic aminopolyols, and its microgram-scale application to an aminobacteriohopanetriol is presented.

Oligosaccharide microscale analysis by circular dichroic spectroscopy: Reference spectra for chromophoric d-fructofuranoside derivatives

The microscale analytical method that is being developed in this group for the structure determination of oligosaccharides yields monosaccharide derivatives bearing two types of chromophores suitable for exciton-coupling, namely, 4-bromobenzoate (lambda max 245 nm) and 4-methoxycinnamate (lambda max 311 nm). Comparison of the circular dichroic (CD) curves of these subunits to those in the reference library allows for the determination of the sugar identities, linkage positions, and the absolute configurations. The 32 possible derivatives of methyl alpha- and beta-D-fructofuranosides bearing four chromophores were prepared and their CD spectra recorded. These data serve to extend the CD library, which already encompasses pyranoside derivatives with the gluco-, galacto-, and manno-configurations, and extend the utility of this methodology to the analysis of fructose-containing oligosaccharides.

Structure Determination of Saponins with Cardiotonic Activity by Circular Dichroism

Cardenolides including ouabain and digoxin are plant steroids that occur in nature as glycosides. They exhibit powerful cardiotonic activity by inhibiting Na+,K+-ATPase (the sodium pump) in mammalian and insect cells and as such have long been used for the treatment of certain cardiac disorders. The chemical structures of cardenolides are characterized by 3-β-OH (or 3β-O-sugar), C/D—cis-ring juncture, 14β-OH, and 17β-unsaturated lactone ring (Figure 1) [1,2]. Most of the sugars isolated after hydrolysis of cardiac glycosides are unique and have only rarely been found elsewhere in nature. Based on optical rotation data it was suggested that all natural cardiac glycosides of D(L) -sugars are β(α) glycosides at the aglycone-sugar linkage. Although the cardenolides have been mostly purified from plants and toads, their conserved and specific binding site located on the catalytic sub-unit of the mammalian plasma membrane sodium pump led to the speculation that there might exist the mammalian counterparts of cardenolides. that control the physiological functions of sodium pump[1,3].