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

The scabrosin esters (1)-(4), isolated from the lichen Xanthoparmelia scabr osa, were reanalysed by modern one- and two-dimensional n.m.r. spectroscopi c methods, including N-15 n.m.r. spectroscopy, and single-crystal X-ray str uctural analysis. This reinvestigation has resulted in the unambiguous stru cture 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 isola ted and its structure determined, including assignment of absolute configur ation. Several scabrosins were found to exhibit potent cytotoxic activity a gainst the murine P815 mastocytomia cell line (IC50 c. 0.5 mu M) and the hu man breast MCF7 carcinoma cell line (IC50 c. 1 nM). Compounds which contain a dithiopiperazinedione moiety have not previously been identified in lich enized fungi.