Cytotoxic Limonoids from the Twigs and Leaves of Toona ciliata.

ABSTRACT

Eight new limonoids, toononoids A-H (1-8), eight new B-seco-29-norlimonoids, toonanoronoids A-H (9-16), and seven known analogues were obtained from the EtOAc extract of the twigs and leaves of Toona ciliata. Compounds 2, 4, 8, and 16 are rare lactam-bearing limonoids. Compounds 1, 14, and 15 possess an unusual γ-methoxybutenolide moiety at C-17, while compounds 9, 10, and 15 have a rare 3ß-hydroxy group. Their 2D structure and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 9, 14, and 15 were established via X-ray diffraction crystallography or comparison of experimental and calculated ECD data. The cytotoxicity of the compounds was assessed toward five human tumor cell lines, and their anti-inflammatory activity was assessed based on NO production using LPS-stimulated RAW264.7 macrophages. Compounds 11 and 12 exerted inhibition toward two tumor cell lines (MCF-7, SW-480) with IC50 values between 2.1 and 3.7 µM, while 18-22 inhibited the proliferation of HL-60, MCF-7, and SW-480 cells (IC50 0.6-4.0 µM). Only compound 4 exhibited weak anti-inflammatory activity with an IC50 value of 28.3 µM.