| An investigation of Callicarpa americana L. as a source of anticancer natural products was carried out using bioassay-guided isolation techniques, leading to the isolation of six new compounds and eight known compounds from the chloroform extract of the combined fruits, leaves, and twigs of Callicarpa americana L (Lamiaceae). The structures of the new compounds were elucidated as 12(S),16xi-dihydroxycleroda-3,13-lien-15,16-olide, 12(S)-hydroxy-16xi-methoxycleroda-3,13-dien-15,16-olide, 12(S)-hydroxy cleroda-3,13-dien-15,16-olide, 16xi-hydroxycleroda-3,11( E),13-trien-15,16-olide, 3beta,12(S)-dihydroxy-cleroda-4(18),13-dien-15,16-olide, and 12(S)-hydroxycleroda-3,13-dien-16,15-olide using a range of spectroscopic techniques, including 1D and 2D NMR, UV, IR, the Mosher ester technique, and accurate mass measurement. Of the known compounds, calliterpenone, euscaphic acid, and salvigenin (6,7-dimethoxy-4'-hydroxyflavone) were previously reported to occur in the genus Callicarpa, and genkwanin (5,4'-hydroxy-7-methoxyflavone), 16xi-hydroxycleroda-3,13-dien-15,16-olide, 5-hydroxy-7,4'-dimethoxyflavone, 3beta,16xi-di-hydroxycleroda-4(18),13-dien-15,16-olide, and 2-formyl-16xi-hydroxy-3-A-norcleroda-2,13-dien-15,16-olide are reported for the first time from Callicarpa in this study.;The isolates obtained were tested for cytotoxicity in a panel of human cancer cell lines. Genkwanin, 12(S),16xi-dihydroxycleroda-3,13-dien-15,16-olide, 16xi-hydroxycleroda-3,11(E),13-trien-15,16-olide, 16xi-hydroxycleroda-3,13-dien-15,16-olide, 2-formyl-16xi-hydroxy-3-A-norcleroda-2,13-dien-15,16-olide, and 12(S)-hydroxycleroda-3,13-dien-16,15-glide all showed cytotoxic activity below 5 mug/mL in at least one cell line against which they were tested.;12(S),16xi-Dihydroxycleroda-3,13-dien-15,16-olide was tested in an in vivo model of antitumor activity against hormone-dependent prostate cancer (LNCaP), human lung cancer (Lu1), and hormone-dependent breast cancer (MCF-7) cell lines using the hollow fiber assay. This isolate was tested at 6.25, 12.5, 25, and 50 mg/kg in mice, administered via intraperitoneal injection. 12(S),16xi-Dihydroxycleroda-3,13-dien-15,16-olide was not active against the cancer cells, even at the highest dose tested (50 mg/kg), but two of three mice died at each of the two highest doses.;In addition to the biological activity discussed above, the isolates identified suggested a taxonomic affiliation of the genus Callicarpa with other members of the mint family of plants (Lamiaceae). |
