Cytotoxic diterpenes from roots of Crossopetalum gaumeri, a Celastraceae species from Yucatan Peninsula

Bioorg Med Chem Lett. 2014 May 1;24(9):2105-9. doi: 10.1016/j.bmcl.2014.03.051. Epub 2014 Mar 26.

Abstract

Four new diterpenes, crossogumerins A-D (1-4) along with six known ones (5-10) were isolated from the root bark of Crossopetalum gaumeri, an endemic medicinal plant from the Yucatan Peninsula. Their structures were elucidated on the basis of 1D and 2D NMR techniques, including HMQC, HMBC, and ROESY experiments. Compounds 1-5, 8-10 were evaluated for cytotoxicity against HeLa (carcinoma of the cervix) and Hep-2 (lung carcinoma) human tumor cells lines and against normal Vero cells (African green monkey kidney) in lag and log phase of growth. Podocarpane diterpenes, crossogumerin B (2) and nimbiol (10), exhibited the highest activity against HeLa cells (IC50 values of 3.1 and 8.1 μM, respectively), but also selectivity on Vero cells (SI 22.6 and 7.5, respectively). The preliminary SAR studies suggest that an epoxy moiety in ring B and a hydrogen bond-donor group strategically positioned in the diterpene core are important requirements for cytotoxicity and selectivity.

Keywords: Celastraceae; Crossopetalum; Cytotoxicity; Podocarpane; Yucatán.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Celastraceae / chemistry*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Diterpenes / chemistry*
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • HeLa Cells
  • Humans
  • Neoplasms / drug therapy
  • Plant Roots / chemistry
  • Vero Cells

Substances

  • Antineoplastic Agents, Phytogenic
  • Diterpenes