Isolation, structure determination and biological activities of a novel antifungal antibiotic, S-632-C, closely related to glutarimide antibiotics.

Abstract

A new antifungal antibiotic, S-632-C, was extracted with ethyl acetate from the culture filtrate of Streptomyces hygroscopicus S-632 and isolated through a combination of column and preparative thin-layer chromatographies on silica gel. The structure of S-632-C was determined by analysis of 1H and 13C-NMR, MS, UV and IR spectra in comparison with those of S-632-A2 (9-methylstreptimidone). The signals were assigned on the basis of 2D NMR experiments, which involved 1H-1H DQF COSY, HMQC and HMBC spectral analysis. From these results, the chemical structure of S-632-C was elucidated as 6-(3,5-dimethyl-2-oxo-4,6-octadienyl)-4-carbamoylmethyl-3,4, 5,6-tetrahydro-2- pyrone. The antibiotic exhibited exclusively weak in vitro antifungal activity against Saccharomyces spp. and similar cytotoxic activity against KB carcinoma cells, as compared with the glutarimide antibiotic S-632-A2. In addition, this antibiotic had the ability to change the morphology of ras(ts)-transformed NRK cells to that of normal cells, also a characteristic S-632-A2 and B1.