Two new limonoids, 12-ethoxynimbolinins G and H (compounds 1 and 2), and one known compound, toosendanin (Chuanliansu) (compound 3), were isolated from the bark of Melia toosendan. Their structures were elucidated by spectroscopic analysis and X-ray techniques. The absolute configuration of toosendanin (3) was established by single-crystal X-ray diffraction. Compounds 1-3 were evaluated for their cytotoxicity against five tumor cell lines.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Limonins ; isolation & purification ; Melia ; chemistry ; Molecular Structure ; Plant Bark ; chemistry ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; X-Ray Diffraction

Podophyllotoxone (1) was isolated from the roots of Dysosma versipellis. The structure was determined by spectroscopic analysis in combination with single-crystal X-ray analysis. The absolute configuration of compound 1 was assigned based on the Flack parameter. It showed significant inhibitory activities against human prostate cancer cells PC3 and DU145 with IC50 values being 14.7 and 20.6 μmol·L(-1), respectively. It also arrested the cells at G2/M phase. Tubulin polymerization assay showed that it inhibited the tubulin polymerization in a dose-dependent manner, and molecular docking analysis revealed a different binding mode with tubulin as compared with those known tubulin inhibitors.
Antineoplastic Agents ; chemistry ; pharmacology ; Berberidaceae ; chemistry ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; G2 Phase ; drug effects ; Humans ; Hydrogen Bonding ; drug effects ; Male ; Molecular Conformation ; Molecular Docking Simulation ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; Plant Roots ; chemistry ; Podophyllotoxin ; chemistry ; pharmacology ; Polymerization ; Prostatic Neoplasms ; drug therapy ; Tubulin ; drug effects ; Tubulin Modulators ; pharmacology