WS-7528

WS-7528, produced by Streptomyces sp. No. 7528, was extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as pale yellow powder (C16H14O5, mp 95-98 degrees C). WS-7528 inhibited estrogen binding to its receptor protein in rat uterine cytosol. The IC50 value of WS-7528 for partially purified rat uterine cytosol receptor was 5.7 x 10(-8) M. This compound was found to induce the growth of the estrogen dependent cell line MCF-7. WS-7528 was tested orally and subcutaneously in immature rats to confirm its effect on the growth of the uterus. WS-7528 has also weak anti-inflammatory activity on the carrageenin paw edema of the rat model.

Streptomyces graminofaciens BA14348, isolated from a soil sample, was found to produce new specific inhibitors of estrogen binding to its receptor. Five related substances, BE-14348A approximately E, were isolated, and their structures were determined by analyses of spectral properties. Of these substances, A was identical with the known flavanone, naringenin. On the other hand, B, C, D and E were all new compounds; the structure of B was determined to be 2(S): 3(S)-3-methyl-4',5,7-trihydroxyflavanone, C was a racemic mixture of 2(S): 3 (R) and 2(R): 3(S)-3-methyl-4',5,7-trihydroxyflavanone; D and E were 8-chloro derivatives of B and C, respectively.