Two New Cytotoxic Maytansinoids Targeting Tubulin from Trewia nudiflora.

Two new maytansinoids, N -methyltreflorine (1) and methyltrewiasine (2), were isolated from the dried fruits of Trewia nudiflora , together with three known congeners (3 – 5). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1 and 2 was determined by X-ray crystallographic analysis. Compounds 1 – 5 exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 – 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1 and 4 also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1 and 2 significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively. [ABSTRACT FROM AUTHOR]