Corymbulosins I-W, Cytotoxic Clerodane Diterpenes from the Bark of Laetia corymbulosa

J Org Chem. 2018 Jan 19;83(2):951-963. doi: 10.1021/acs.joc.7b02951. Epub 2018 Jan 10.

Abstract

The isolation studies of a crude MeOH/CH2Cl2 (1:1) extract (N005829) of the bark of Laetia corymbulosa yielded 15 new clerodane diterpenes, designated corymbulosins I-W (1-15), as well as four known diterpenes, 16-19. The structures of 1-15 were characterized on the basis of extensive 1D and 2D NMR and HRMS analyses. The absolute configurations of newly isolated compounds 1-15, as well as known 16-19, which were reported previously with only relative configurations, were determined through ECD experiments, X-ray analysis, chemical methods, including Mosher esterification, and comparison of their spectroscopic data. The isolated compounds were evaluated for cytotoxicity against human cancer cell lines. Flow cytometric and immunocytochemical observations of cells treated with cytotoxic clerodanes demonstrated that the chromatin was fragmented and dispersed with formation of apoptotic microtubules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diterpenes, Clerodane / chemistry
  • Diterpenes, Clerodane / isolation & purification
  • Diterpenes, Clerodane / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Plant Bark / chemistry*
  • Salicaceae / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Diterpenes, Clerodane