Studies on the cytotoxicity of asterriquinone derivatives.

The antitumor agent, asterriquinone (ARQ) is a known metabolite isolated from the mycelium of Aspergillus terreus IFO 61231). YAMAMOTO et al. reported that ARQ analogues having a 2, 5-dimethoxy-p-benzoquinone moiety (ARQ dimethyl ether: ARQDMe)2,3) and the 2, 5-diamino-p-benzoquinone moiety (diamino ARQ: ARQDA)4) did not show any Cytotoxicity. As reported in our previous communication5), a new metabolite, asterridinone, which has a furo [3, 2-b] furan moiety instead of the p-benzoquinone moiety of ARQ, did not show cytotoxic activity towards P388 mouse leukemia cells, while isoasterriquinone and neoasterriquinone which have the tertor iso-pentenyl groups at the different position of the indole ring, were active as was ARQ. These results indicate that the 2, 5-dihydroxy-p-benzoquinone structure is more important for cytotoxic activity than the kind of prenyl groups and its position. In this study, to assess the contribution of the hydroxy group in the p-benzoquinone moiety to the cytotoxic activity of ARQ, we synthesized several ARQ derivatives, of which the one or two hydroxy group(s) were substituted with the acetyl, methoxy, and/or amino groups, and examined their cytotoxicity towards P388 cells.