title: Exposure of chlorpromazine to 266 nm laser beam generates new species with antibacterial properties: contributions to development of a new process for drug discovery.
abstract: BACKGROUND
  Phenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser.
  
  
  METHODS
  Varying concentrations of Chlorpromazine Hydrochloride (CPZ) (2-20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1-24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200-1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC)-Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923.
  
  
  RESULTS
  CPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified.
  
  
  CONCLUSIONS
  Exposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is "clean" and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives.
authors: Laser Department, National Institute for Laser, Plasma and Radiation Physics, Magurele/Ilfov, Romania. mihai.pascu@inflpr.ro
authors: Mihail Lucian
authors: ML
authors: Pascu
authors: Balazs
authors: B
authors: Danko
authors: Ana
authors: A
authors: Martins
authors: Nikoletta
authors: N
authors: Jedlinszki
authors: Tatiana
authors: T
authors: Alexandru
authors: Viorel
authors: V
authors: Nastasa
authors: Mihai
authors: M
authors: Boni
authors: Andra
authors: A
authors: Militaru
authors: Ionut Relu
authors: IR
authors: Andrei
authors: Angela
authors: A
authors: Staicu
authors: Attila
authors: A
authors: Hunyadi
authors: Seamus
authors: S
authors: Fanning
authors: Leonard
authors: L
authors: Amaral
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000528:radiation effects; D002746:Chlorpromazine / Q000031:analogs & derivatives / Q000528:radiation effects*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D018492:Dopamine Antagonists / Q000528:radiation effects*; D055808:Drug Discovery; D007834:Lasers; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D018492:Dopamine Antagonists; D002746:Chlorpromazine