benanomicin-a and Mycoses

A number of substances that directly or indirectly affect the cell walls of fungi have been identified. Those that actively interfere with the synthesis or degradation of polysaccharide components share the property of being produced by soil microbes as secondary metabolites. Compounds specifically interfering with chitin or beta-glucan synthesis have proven effective in studies of preclinical models of mycoses, though they appear to have a restricted spectrum of coverage. Semisynthetic derivatives of some of the natural products have offered improvements in activity, toxicology, or pharmacokinetic behavior. Compounds which act on the cell wall indirectly or by a secondary mechanism of action, such as the azoles, act against diverse fungi but are usually fungistatic in nature. Overall, these compounds are attractive candidates for further development.

Topics: Aminoglycosides; Amphotericin B; Animals; Anthracyclines; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Cell Wall; Chitin; Echinocandins; Fungal Proteins; Fungi; Glucans; Mice; Mycoses; Peptides; Peptides, Cyclic; Pyrimidine Nucleosides

The in-vivo antifungal activity of benanomicin A administered intravenously or subcutaneously was compared with that of amphotericin B and fluconazole using animal models of systemic infections with Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The efficacy of benanomicin A in C. albicans infection was more pronounced when administered in multiple doses than in a single dose. This was also true of fluconazole, but not of amphotericin B, which showed no difference between single and multiple dosings. Benanomcin A eradicated C. albicans cells from the kidneys of infected mice in a manner comparable to that of amphotericin B, but more effectively than fluconazole. The histopathological findings obtained from the kidneys of the C. albicans-infected mice confirmed the therapeutic efficacy of benanomicin A. The subcutaneous ED50 values of benanomicin A were 1.30 mg/kg/day (C. albicans) and 19.0 mg/kg/day (A. fumigatus) which were intermediate between those of amphotericin B and fluconazole in the two models. The subcutaneous ED50 value of benanomicin A for C. neoformans was 21.5 mg/kg/day, which was higher than that of amphotericin B.

Topics: Amphotericin B; Animals; Anthracyclines; Antibiotics, Antineoplastic; Antifungal Agents; Aspergillosis; Candidiasis; Cryptococcosis; Cryptococcus neoformans; Female; Fluconazole; Kidney; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Mycoses