Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (-) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (-) are reported as isolated from C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds , , , and exhibited significant cytotoxicity against H23 cell line with IC values of 6.9, 6.4, 3.9, and 2.6 μM, respectively.