Synthesis and biological evaluation of analogs of altohyrtin C (spongistatin 2)

Several structural analogs that contain only part of the altohyrtin structure have been prepared and compared with synthetic altohyrtin C (2) for in vitro cytotoxicity against human colon (HCT116) and ovarian (A2780) cell lines. Whereas altohyrtin C was found to be exceedingly potent against these lines (IC50=0.0003 μM), analogs 3–5 were >27,000-fold less potent (IC50>8 μM). Analogs 6 and 7 also demonstrated weak cytotoxicity with IC50 values for the HCT116 and A2780 cells of 4.8 μM and 2.4 μM, respectively, for 6.