Two New Cytotoxic Maytansinoids Targeting Tubulin from Trewia nudiflora

Planta Med. 2022 Jul;88(8):678-684. doi: 10.1055/a-1530-1128. Epub 2021 Oct 29.

Abstract

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.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Tubulin* / chemistry
  • Tubulin* / metabolism

Substances

  • Antineoplastic Agents
  • Tubulin