Rapid identification of cyclic tetrapyrrolic photosensitisers for photodynamic therapy using on-line hyphenated LC-PDA-MS coupled with photo-cytotoxicity assay

Phytochem Anal. 2012 Jan-Feb;23(1):52-9. doi: 10.1002/pca.1324. Epub 2011 Jun 21.

Abstract

Introduction: Photodynamic therapy is a treatment modality that involves site-directed generation of cytotoxic reactive oxygen species by light-activated photosensitisers.

Objective: In order to rapidly identify new photosensitisers from natural extracts, we developed a liquid chromatography-photodiode array-mass spectrometry (LC-PDA-MS) method to rapidly identify plant extracts that contain photosensitisers, particularly those possessing a cyclic tetrapyrrole structure.

Method: Six previously isolated compounds (1-6) were identified in bioactive fractions derived from 15 plant extracts on the basis of their chromatographic retention times, UV-visible profiles, accurate mass and fragmentation patterns.

Results: Samples containing uncommon photosensitisers were rapidly identified using this method, and subsequent scale-up isolation efforts led to two new compounds (7 and 8) which were confirmed to be active photosensitisers in a photo-cytotoxicity assay.

Conclusion: This method serves as a useful tool in prioritising samples that may contain new photosensitisers out of a larger group of photo-cytotoxic natural products extracts.

MeSH terms

  • Biological Assay
  • Cell Survival / drug effects
  • Chromatography, Liquid / methods*
  • HL-60 Cells
  • Humans
  • Malaysia
  • Mass Spectrometry / methods*
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / isolation & purification*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / radiation effects
  • Plant Bark / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification*
  • Plant Extracts / pharmacology
  • Plant Extracts / radiation effects
  • Plant Leaves / chemistry
  • Plant Stems / chemistry
  • Plants / chemistry*
  • Tetrapyrroles / chemistry
  • Tetrapyrroles / isolation & purification*
  • Tetrapyrroles / pharmacology

Substances

  • Photosensitizing Agents
  • Plant Extracts
  • Tetrapyrroles