SAR study of a novel triene-ansamycin group compound, quinotrierixin, and related compounds, as inhibitors of ER stress-induced XBP1 activation - I. Taxonomy, fermentation, isolation, biological activities and SAR study

In the course of screening for an inhibitor of ER stress-induced XBP1 activation, we isolated a new member of the triene-ansamycin group compound, quinotrierixin, from a culture broth of Streptomyces sp. PAE37. Quinotrierixin inhibited thapsigargin-induced XBP1 activation in HeLa cells with an IC(50) of 0.067 mu M. We found that other triene-ansamycin group compounds such as demethyltrienomycin A and mycotrienin I also inhibited ER stress-induced XBP1 activation. Moreover, we performed SAR study of twelve triene-ansamycin group compounds. The study showed that OH group at C-13 was crucial, and CH(3) group at C-14 would be important for the XBP1 inhibitory activity.