Highly Oxygenated Limonoids and Lignans from Phyllanthus flexuosus

Two new highly oxygenated limonoids, flexuosoids A (1) and B (2), and three new arylnaphthalene lignan glycosides, phyllanthusmins D-F (3-5), were isolated from the roots of Phyllanthus flexuosus, in addition to three known lignans, phyllanthusmin C, arabelline, and (+)-diasyringaresinol. Their structures were elucidated on the basis of detailed spectroscopic analysis and chemical methods. Compounds 1 and 2, two new decaoxygenated limonoids with a C-19/29 lactol bridge and heptaoxygenated substituents at C-1, C-2, C-3, C-7, C-11, C-17, and C-30, represent the second example of limonoids in the Euphorbiaceae family. Most of the isolates were tested for their antifeedant, anti-herpes simplex virus 1, and cytotoxic activities. The new limonoids 1 and 2 showed promising antifeedant activity against the beet army worm (Spodoptera exigua) with EC50 values of 25.1 and 17.3 mu g/cm(2), respectively. In addition, both of them displayed moderate cytotoxicity against the ECA109 human esophagus cancer cell line, along with the known lignan glycoside, phyllanthusmin C, with the IC50 values of 11.5 (1), 8.5 (2), and 7.8 (phyllanthusmin C) mu M, respectively.