Nine triterpenes with antiviral activity against Herpes simplex virus types I and II in vitro were isolated from dammar resin. Each compound caused a significant reduction in viral cytopathic effect when Vero cells were exposed continuously to 1-10 micrograms/ml of compound for 48 h after viral challenge. The triterpenes were identified as dammaradienol [1], dammarenediol-II [2], hydroxydammarenone-I [3], ursonic acid [5], hydroxyhopanone [11], dammarenolic acid [15], shoreic acid [16], eichlerianic acid [17], and a novel compound, hydroxyoleanonic lactone [7], on the basis of their chromatographic, spectroscopic, and physical properties.
A new glycopeptide antibiotic complex was isolated from the fermentation culture of Kibdelosporangium aridum subsp. largum (SK&F AAD-609) by affinity chromatography on a D-alanyl-D-alanine agarose column. The major components of the complex were resolved by preparative reversed-phase HPLC. Mild acid hydrolysis showed that the new antibiotics have the same mannosyl aglycon (2) as the aridicins.FAB mass spectrometry, isoelectric focusing, potentiometric titration and carbohydrate and fatty acid analyses were used to determine the structures of the five major components of the complex. These studies showed that the kibdelins differ from the aridicins only in the oxidation level at the C-6 position of the amino sugar. Kibdelin A (5), B (6), C, (7), C2 (8) and D (9) are a series of N-acylglucosamine analogs containing saturated straight and branched chain C,,-C,; fatty acids whereas, in kibdelin D the fatty acid component is (Z)-4-decenoic acid.
An extensive taxonomic investigation identified strain SK&F-AAJ-271 as a newspecies, designated Actinomadura parvosata. Fermentations of this organism produce a complex of acidic, lipophilic glycopeptide antibiotics, the parvodicins. Structures for seven of the isolated components were derived from a combination of mass spectral, high-field NMRand chemical techniques. The O-acetyl functionality present in two of the isolated components is a structural feature unique amongthe knownmembersof this class of antibiotics. The parvodicins are active in vitro against a range of Gram-positive bacteria. The most active parvodicin, Q, produces high serum levels in vivo and has the potential for a long duration of action.The increasing importance of vancomycin for the treatment of methicillin-resistant staphylococcal infections1*10 has stimulated the search for novel membersof this class of glycopeptide antibiotics. Central to our effort in this area has been a mechanism-based screen3) in which a mimetic of the bacterial cell wall receptor4) for glycopeptides is used to antagonize selectively the activity of these antibiotics in the complex mixture of culture products, the implementation of efficient isolation and purification procedures,5>6) as well as the development of fast atom bombardment mass spectrometry (FAB-MS) techniques7) and modern two-dimensional (2D) NMRmethods8) for structural characterization. This strategy has led to the discovery, isolation and structure elucidation of the aridicins,8~10) the kibdelins11'125 and as reported in detail here, the parvodicins.13)
Materials and Methods
Chemotaxonomy, Physiological and Biochemical EvaluationStrain SK&F-AAJ-271 was isolated from a soil sample collected on the shore of a pond or stream near Myittanyunt, Burma. Because SK&F-AAJ-271sporulates poorly, the culture was grown in shake flasks and maintained as frozen stock in a mechanical freezer at -70°C or in the vapor phase of liquid nitrogen. Slant cultures were maintained on thin inorganic salts -starch agar (Difco inorganic salts -starch agar (ISP 4) 12 g, Difco Bactoagar 15 g, distilled water (1 liter) supplemented with yeast extract (2 g/liter)). Morphological observations were made on plates of modified thin inorganic saltsstarch agar (Difco inorganic salts -starch agar (ISP 4) 12 g, Difco Bactoagar 15 g, distilled water 800 ml, soil extract 200 ml, thiamine hydrochloride 0.5 mg, biotin 0.25 mg). Color descriptions were chosen by comparison to color chips from the ISCC-NBSColor Charts14) or the Methuen Handbook of
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