Falconensones A and B are a new type of yellow pigment with structural similarity to
retinoic acid isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis or Emericella fruticulosa. In the present study we show that
falconensone A alone induced apoptosis of HL60 human
leukemia cells, while
falconensone B, the 4'-nor-methyl derivative of
falconensone A, had much lower activity. The synthetic derivatives of
falconensone A,
falconensone A p-bromophenylhydrazone and
falconensone A dioxime, were more potent than natural
falconensone A and B as far as the induction of apoptosis was concerned. The induction of apoptosis by the falconensones correlated with their inhibition of cell growth. In addition, falconensones A and B, and
falconensone A dioxime, increased the generation of intracellular
reactive oxygen species, while
falconensone A p-bromophenylhydrazone was inactive. These results suggest that
falconensone A,
falconensone A p-bromophenylhydrazone and
falconensone A dioxime are potential new apoptosis-inducing agents. The enhanced generation of
reactive oxygen species in cells may be involved in apoptosis induced by
falconensone A and
falconensone A dioxime, but not by
falconensone A p-bromophenylhydrazone. It is also suggested that the methyl residue at the 4' position of the
falconensone A cyclopentenone ring may be essential for the induction of apoptosis. Based on these results,
falconensone A and its derivatives may be clinically useful in the treatment of some
leukemias.