PRADIMICINS A, B AND C: NEW ANTIFUNGAL ANTIBIOTICS

II. IN VITRO AND IN VIVO BIOLOGICAL ACTIVITIES

抄録

Pradimicins A, B and C specify novel antibiotics produced by Actinomadura hibisca No. P157-2 (ATCC 53557) possessing potent and broad antifungal activity in vivo. They showed moderate in vitro antifungal activity against a wide variety of fungi and yeasts including clinically important pathogens, and were highly effective in systemic infection with Candida albicans in mice after iv and im administrations. Pradimicin A showed in vivo therapeutic activity against C. albicans, Cryptococcus neoformans and Aspergillus fumigatus in both normal and immunocompromized mice. 5-Fluorocytosine- and azole-resistant C. albicans strains were susceptible to pradimicin A. This antibiotic also demonstrated therapeutic efficacy against lung candidiasis and aspergillosis, vaginal candidiasis and skin Trichophyton mentagrophytes infection in mice with iv or topical treatment. The LD₅₀ values after a single iv or im administration were 120mg/kg and more than 400mg/kg, respectively. Against various cultured mammalian cells, pradimicin A was noncytotoxic at 100 or 500μg/ml, and showed potent anti-influenza virus activity with an IC₅₀ value of 6.8μg/ml.