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

IntroductionPhenothiazines 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.MethodsVarying 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.ResultsCPZ 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.ConclusionsExposure 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.

Surface properties of Vancomycin after interaction with laser beams

“…This study aims to identify methods and means to obtain solutions samples containing VCM as parent compound and photoproducts obtained out of it by exposure to UV laser radiation, so that the samples contain small amounts of photoproducts with efficient antibacterial properties and lower overall toxicity. In this direction, photoproducts with enhanced antibacterial activity with respect to the parental compound were reported when Chlorpromazine is exposed to laser radiation [9]. This paper shows results about the laser beams interaction with VCM solutions in ultrapure water performed in bulk samples (5 mL), based on earlier reports introduced in [10].…”

“…On the other hand, the use of lasers as sources of electromagnetic radiation in order to generate out of existing medicines small amounts of new photoproducts which may be efficient in fighting multiple drug resistance developed by bacteria (MDR) is one of the most actual and promising methods in this field [9,10].…”

The Role of Efflux Pumps and Environmental pH in Bacterial Multidrug Resistance

“…In the case of PMZ the solvent for the stock solution was distilled water. Phenothiazines are affected by light, thus, PMZ was protected from it (15). The optical properties of the broth with and without PMZ were not altered.…”

Toxicity study in blood and tumor cells of laser produced medicines for application in fabrics

“…The set-up utilized to study the stability of the irradiated phenothiazines solutions is shown in Fig.1a where a variant of a more general system described in [3,4] is drawn.…”

“…Recent reports have shown that phenothiazines solutions as parent compounds, when exposed to ultraviolet (UV) laser radiation generate photoproducts that have different molecular structures and properties with respect to them [1][2][3][4]. More recent studies show that solutions of phenothiazines in water once exposed to laser radiation have modified wetting properties with respect to fabrics [5].…”