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The structures of potent cytotoxic cycloheptapeptides, mallotumides A-C ( 1 - 3 , respectively) isolated from the roots of Mallotus spodocarpus Airy Shaw, were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by single-crystal X-ray crystallographic data. All three cycloheptapeptides exhibited potent cytotoxicity against various cancer cell lines with IC 50 values ranging from 0.60 to 4.02 nM.

VR-3848, a novel peptide derived from Euphobiaceae, is shown herein to induce apoptosis at nanomolar concentrations in the leukemic Jurkat cell line. Apoptosis was associated with activation of caspases, release of cytochrome c from mitochondria, fragmentation of nuclear DNA, and externalization of phosphatidylserine on the cell surface. Overexpression of mitochondria-targeted Bcl-2 abrogated VR-3848-induced killing in this model. Primary human interleukin (IL)-2-activated T lymphocytes were considerably less sensitive to VR-3848-induced apoptosis as compared to Jurkat cells. VR-3848 thus holds the promise of being a potent and selective anti-cancer agent that deserves further exploration.