Structure revision and cytotoxic activity of the scabrosin esters, epidithiopiperazinediones from the lichen Xanthoparmelia scabrosa

Abstract

The scabrosin esters (1)-(4), isolated from the lichen Xanthoparmelia scabrosa, were reanalysed by modern one- and two-dimensional n.m.r. spectroscopic methods, including 51N n.m.r. spectroscopy, and single-crystal X-ray structural analysis. This reinvestigation has resulted in the unambiguous structure elucidation and complete spectral assignment of these metabolites and established them to be a family of epidithiopiperazinedione derivatives. A new scabrosin ester, scabrosin butyrate hexanoate (5), has also been isolated and its structure determined, including assignment of absolute configuration. Several scabrosins were found to exhibit potent cytotoxic activity against the murine P815 mastocytomia cell line (IC50 c. 0.5 μM) and the human breast MCF7 carcinoma cell line (IC50 c. 1 nM). Compounds which contain a dithiopiperazinedione moiety have not previously been identified in lichenized fungi.