Ansamycin derivatives from the marine-derived Streptomyces sp. SCSGAA 0027 and their cytotoxic and antiviral activities

Fourteen ansamycin derivatives including seven new herbimycins G-L (1-6) and divergolide O (7), and seven known analogues were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their complete structures were determined by detailed analysis of spectroscopic data and quantum chemical calculations. Compounds 1-5 and 7 featured an additional eight-membered O-heterocycle that has rarely been reported for ansamycins, and the Z,Z- and E,E-configurations for Delta(2),Delta(4) were reported for the first time in geldanamycin analogues. Compound 1 exhibited weak inhibition activity towards Hsp90 alpha with an IC50 value of 96 mu M, 2-5 showed mild cytotoxicity against four human cancer cell lines with IC50 values ranging from 13 mu M to 86 mu M, and 7 had moderate anti-HSV-1 activity with an IC50 value of 19 mu M and very weak cytotoxicity towards Vero cell. The possible biosynthetic pathways for 1-5 were proposed. And their structure-bioactivity relationship was also discussed.