Studies on synergisidin.

Penicillium sp. No. Y-11930 was isolated from soil sample collected at Shimouma, Setagaya, Tokyo in September 1978. Synergisidin produced by the strain was obtained with high yield in starch-corn steep liquor medium, extracted with ethyl acetate at pH 5.0 and crystallized from ethyl acetate after decolorization with active charcoal. The antibacterial activities of synergisidin against Gram-positive and Gram-negative bacteria and Mycobacterium were almost nothing but synergisidin showed weak activities against eumycetes with MICs of 6.25-100 microgram/ml. However, synergidisin was confirmed and discovered to show 30-125-fold strong synergistic effects against Candida sp. in particular with addition to extremely small quantities of imidazole antimycotics such as econazole, miconazole and clotrimazole. The acute toxicity was LD50 smaller than or equal to 250 mg/kg in mice (i.p.). the morphological degenerative effect on HeLA cells was observed in concentrations of more than 0.122 microgram/ml. The chemical structure of synergisidin was estimated as 7, 16-dihydroxy-2-methyl-4-oxo-3-oxabicyclo [10. 3. 1] hexadeca-5, 10-diene or 2, 15-dihydroxy-7-methyl-5-oxo-6-oxabicyclo (11. 3. 0] hexadeca-3, 11-diene (the same structure as decumbin, brefeldin A and ascotoxin) from various physiochemical properties but later, comparison with brefeldin A and ascotoxin revealed that synergisidin was identical with those.