SAR studies on hydropentalene derivatives—Important core units of biologically active tetramic acid macrolactams and ptychanolides

Abstract Structurallydiverse bicyclo[3.3.0]octanes were prepared and tested for their biological activity. Both the antiproliferative activity and the results of phenotypic characterization varied with the substitution patterns. Two derivatives displayed high inhibitory (IC 50 ⩽3 μM) activity against the L-929 cell line, but differed in their modeof action. A cluster analysis with impedance profiling data showed the two compounds in relationship to microtubule interfering compounds. In PtK 2 cells treated with both derivatives a perturbing effect on the microtubular network was observed, whereas the actin cytoskeleton in incubated PtK 2 cells was disturbed only by one compound. The effects on tubulin and actin polymerization could be confirmed by in vitro polymerization experiments.