Synthesis of solasodine glycoside derivatives and evaluation of their cytotoxic effects on human cancer cells

Drug Discov Ther. 2012 Feb;6(1):9-17.

Abstract

Solasodine glycosides, such as solamargine, have been proved to be very important anti-cancer agents. In order to discover more potent cytotoxic agents and explore the preliminary structure activity relationship, a new series of solasodine glycosides 2-9 were synthesized via a transglycosylation strategy, and their cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562, and PC3 cells) were evaluated by MTT assays. The results indicated that compounds 2, 8, and 9 with the substitute moiety of rhamnose, 2-hydroxyethoxymethyl, and 1,3-dihydroxypropan-2-yloxy-methyl, respectively, exhibited quite strong anticancer activity. The underlying mechanism tests demonstrated that these compounds could induce apoptosis detected by DAPI staining, and Annexin V and propidium iodide binding. Cell cycle analysis indicated that the cancer cells were predominantly arrested at the G2/M phase when exposure to these compounds was examined by flow cytometry. These compounds may serve as lead candidates in the development of novel chemotherapeutics for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Flow Cytometry
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Solanaceous Alkaloids / chemical synthesis
  • Solanaceous Alkaloids / chemistry
  • Solanaceous Alkaloids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Glycosides
  • Solanaceous Alkaloids
  • solasodine