7α,8α-Epoxynagilactones and their glucosides from the twigs of Podocarpus nagi: Isolation, structures, and cytotoxic activities

Fitoterapia. 2018 Mar:125:174-183. doi: 10.1016/j.fitote.2018.01.007. Epub 2018 Feb 2.

Abstract

A phytochemical investigation of twigs of Podocarpus nagi resulted in the identification of eight new type B nagilactones (1-8), all bearing a 7α,8α-epoxy-9(11)-enolide substructure, along with two known analogs (9-10). Their structures were determined on the basis of spectroscopic analysis, including HRESIMS, IR and NMR experiments, and X-ray crystallographic analysis. In vitro cytotoxic assay exhibited that compounds 1, 2, 9 and 10 could induce antiproliferation against three different types of human cancer cells while compounds 3 and 5 were inactive. Notably, the IC50 value of compound 1 is 0.208μM for A431 human epidermoid carcinoma cells, reaching the same level as the positive control combretastatin A-4 (0.104μM). Furthermore, compound 1 performed a strong inhibition of cancer cells by triggering apoptosis and arresting the cell cycle at G1 phase. These results unfold potential anticancer therapeutic applications of type B nagilactones.

Keywords: Apoptosis; Cytotoxic activity; Podocarpus nagi; Type B nagilactone.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • China
  • Drug Screening Assays, Antitumor
  • Glucosides / chemistry*
  • Glucosides / isolation & purification
  • Humans
  • Lactones / chemistry*
  • Lactones / isolation & purification
  • Molecular Structure
  • Pinaceae / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Glucosides
  • Lactones