Abstract
During the search for the hemorrhagic factors from the Fusarium species, we could isolate several toxins other than trichothecenes. Fusarium sambucinum PZF-4 produced an unknown toxin in wheat culture. This toxin, given the trivial name as sambutoxin, was isolated by silica gel chromatography and preparative HPLC. Sambutoxin was elucidated as 3-{5-methyl-6-[E]-1, 3, 5-trimethylhept-1-enyl}tetrahydropyranyl}-5-(p-hydroxyphenyl)-1-methyl-4-hydroxy-2(1H)-pyridone mainly by NMR analyses. Sambutoxin caused toxic effects in rats, including body weight loss, feed refusal, hemorrhage in stomach and intestines, and finally death when rats were fed diets supplemented with 0.05 and 0.1% sambutoxin. It also showed a potent in vitro cytotoxicity against human and mouse tumor cell lines, and the 50% inhibitory dose values ranged from 46 to 174 ng/ml. Fusarium sp. KTTC 16677 from soybean seeds produced apicidin and its derivative, apicidin B. The chemical structure of apicidin B was elucidated as cyclo-[pipecolyl-isoleucyl-(N-methoxy-tryptophan)-(2-amino-8-oxo-3-hydroxy- decanoic acid)] by NMR analyses. Apicidin caused the hemorrhage in stomach and intestines when rats were fed diets supplemented with 0.1 apicidin. Apicidin exhibited acute toxicity with LD50 values of 300 mg/kg by oral and 327 mg/kg by intraperitoneal administration, respectively. Apicidin caused significant cellular electrolyte leakage and chlorophyll reduction in a duckweed bioassay at concentration of 10-100μM. Apicidin also showed in vivo antitumor activity against P388 murine leukemia cell implanted mice with the effective dosages of 30-100 mg/kg by intraperitoneal administration that it produced significant prolongation of survival time of mice with T/C values of 120-148%.
