ABSTRACT
Three new phenylpropanoid glycosides, named luteoside A (3), luteoside B (4), and luteoside C (5), were isolated together with the known compounds verbascoside (1) and isoverbascoside (2) from the roots of the medicinal plant Markhamia lutea. The structures of the new compounds were determined to be 1-O-(3, 4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-4-O- caffeo yl-6-acetyl-beta-d-glucopyranoside, 1-O-(3,4-dihydroxyphenyl)ethyl beta-d-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- caffeo yl-beta-d-glucopyranoside, and 1-O-(3,4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- ferulo yl-beta-d-glucopyranoside, respectively, on the basis of chemical and spectroscopic data. All five phenylpropanoid glycosides exhibited potent in vitro activity against respiratory syncytial virus.
Subject(s)
Antiviral Agents/isolation & purification , Oligosaccharides/isolation & purification , Plants, Medicinal/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Carbohydrate Conformation , Carbohydrate Sequence , Cells, Cultured , Magnetic Resonance Spectroscopy , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Respiratory Syncytial Viruses/drug effects , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
Pneumocandin D0 (9), a new member of the echinocandin class of antifungal agents, has been isolated as a minor constituent from fermentation broths of the filamentous fungi Zalerion arboricola (ATCC 20957). The structure of 9 has been determined mainly on the basis of spectroscopic analysis and by comparison with published data for similar compounds. To date, pneumocandin D0 has been found to be the most potent inhibitor of Pneumocystis carinii development in vivo within the natural-occurring echinocandin family of antifungal agents.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Peptides , Pneumocystis/drug effects , Amino Acid Sequence , Animals , Anti-Bacterial Agents/biosynthesis , Antifungal Agents/biosynthesis , Candidiasis/drug therapy , Echinocandins , Fermentation , Mice , Mice, Inbred Strains , Mitosporic Fungi/metabolism , Molecular Sequence Data , Molecular Structure , Peptides, Cyclic/biosynthesis , Peptides, Cyclic/isolation & purification , Peptides, Cyclic/pharmacology , Pneumonia, Pneumocystis/drug therapy , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
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.
ABSTRACT
HPLC bioautography of the directed biosynthesis of Zalerion arboricola led to the discovery of pneumocandin B0 (L-688,786), a new antifungal and anti-Pneumocystis carinii lipopeptide. Isolation techniques were developed to separate this component from pneumocandin A0 (L-671,329) in fermentations of a mutant of Zalerion arboricola. A number of related compounds were also isolated, which differ from pneumocandins A0 and B0 in the hydroxylation patterns on the ornithine, homotyrosine, and proline.
