Napyradiomycins A and B1: non-steroidal estrogen-receptor antagonists produced by a Streptomyces.

Estrogen-receptor antagonists are used in the therapy of estrogen-responsive diseases including breast cancer and endometrial cancer. Tamoxifen, the non-steroidal estrogen-receptor antagonist, is now the first choice of anti-hormonal treatment for advanced breast cancer. In spite of its effectiveness, the long-term use of tamoxifen frequently results in tumor resistance to itself and its related compounds which have the triphenylethylene moiety. Consideration mentioned above led us to screen microbial products for new non-steroidal estrogen-receptor antagonists without the triphenylethylene moiety. In the previous papers1~3), we reported R1128 substances as novel non-steroidal estrogen-receptor antagonists. In the course of our continuing search for non-steroidal estrogen-receptor antagonists from microbial products, strain No. 9558 was found to produce two estrogen-receptor antagonists. These compounds, named WS9558A and B, were isolated and identified as napyradiomycins A and Bl, respectively4'5). In this paper, we describe new biological and pharmacological properties of napyradiomycins A and Bl. Strain No. 9558 was isolated from a soil sample obtained at Kujukuri-beach, Chiba Prefecture,