Synthesis and cytotoxic activities of usnic acid derivatives

Nine usnic acid–amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and in the PTS deficient CHO-MG cells. In addition, α-difluoromethylornithine, an ornithine decarboxylase inhibitor known to indirectly enhance the activity of the PTS and consequently increase the cytotoxicity of cytotoxic drugs entering cells via the PTS, had no effect on the activity of the polyamine derivatives. The more active derivative (1,8-diaminooctane derivative) displayed similar activities on all cancer cell lines studied and induced apoptosis.

Cytotoxic evaluation of enamines derived from (+)-usnic acid led us to the selection of the diaminooctane derivative as active towards cancer cell lines (2.7 < IC50 < 14.1 μM). Apoptotic effect was also observed.Figure optionsDownload as PowerPoint slide