PNEUMOCANDINS FROM Zalerion arboricola IV. BIOLOGICAL EVALUATION OF NATURAL AND SEMISYNTHETIC PNEUMOCANDINS FOR ACTIVITY AGAINST Pneumocystis carinii AND Candida SPECIES

• Published in: Journal of antibiotics Vol. 45; no. 12; pp. 1886 - 1891
• Main Authors: SCHMATZ, D. M., ABRUZZO, G., POWLES, M. A., MCFADDEN, D. C., BALKOVEC, J. M., BLACK, R. M., NOLLSTADT, K., BARTIZAL, K.
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1992; Japan Antibiotics Research Association
• Subjects: Animals; Anti-Bacterial Agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; beta-Glucans; Biological and medical sciences; Candida albicans - drug effects; Cell Membrane - drug effects; Disease Models, Animal; Echinocandins; Erythrocytes - drug effects; Glucans - metabolism; Hemolysis - drug effects; Humans; Medical sciences; Mice; Microbial Sensitivity Tests; Mitosporic Fungi - chemistry; Peptides; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Pneumocystis - drug effects; Structure-Activity Relationship; Protozoa; Pneumocystis carinii; In vitro; Biological activity; Fungi; In vivo; Antibiotic; Antifungal agent; Structure activity relation; Candida; Fungi Imperfecti; Sporozoa; Thallophyta
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.45.1886

A series of lipopeptide compounds co-produced during the fermentation of pneumocandin A0 (L-671, 329) and related semisynthetic compounds were evaluated in vivo against Pneumocystis carinii pneumonia and systemic candidiasis. In addition, they were tested in vitro against a panel of pathogenic Candida species and in a Candida membrane 1, 3-β-D-glucan synthesis assay. The results of these studies demonstrate that pneumocandin A0 and pneumocandin B0 (L-688, 786) are the most potent compounds when considering both antipneumocystis and anticandida activity. Other compounds in the series are selectively more potent against P. carinii or Candida albicans suggesting a diverging structure-activity relationship. Evaluation of these compounds for their ability to inhibit C. albicans 1, 3-β-D-glucan synthesis in vitro demonstrates that they inhibit this process. A positive correlation between 1, 3-β-D-glucan synthesis inhibition and in vitro antifungal activity was also demonstrated for some of the pneumocandins.