Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation

Pascu, Mihail-Lucian; Nastasa, Viorel; Smarandache, Adriana; Militaru, Andra; Martins, Ana; Viveiros, Miguel; Boni, Mihai; Andrei, Ionuț Relu; Pascu, Alexandru; Staicu, Angela; Molnár, Joséph; Fanning, Séamus; Amaral, Leonard

doi:10.2174/157489111796064515

Cited by 18 publications

(23 citation statements)

References 16 publications

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“…To-date, the multiple drug resistance (MDR) identified for the malignant tumor cells [1][2][3] and bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli etc.) [4] is well documented. With respect to this challenge the science community is asked to find solutions in order to fight MDR and the research efforts may be included in two main categories: (a) development of new medicines and (b) identifying new ways to make efficient again the existing ones.…”

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confidence: 99%

The Laser Use in Generating New Species of Medicines with Antitumor and Antibacterial Properties: New Processes in Drug Discovery

Pascu¹

2012

Biochem & Pharmacol

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EditorialReports made during the last decades, mention the development of drug resistance mechanisms acquired by tumor cells and bacteria. To-date, the multiple drug resistance (MDR) identified for the malignant tumor cells [1][2][3] and bacteria (Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli etc.) [4] is well documented. With respect to this challenge the science community is asked to find solutions in order to fight MDR and the research efforts may be included in two main categories: (a) development of new medicines and (b) identifying new ways to make efficient again the existing ones.The promotion of new medicines is costly, needs sustained efforts and takes long time. Approaching new methods to make the existing medicines efficient in fighting MDR is more convenient, cheaper, faster and simpler, the more so because the medicines utilized to treat particular maladies may become, once modified, efficient in the treatment of completely different illnesses than targeted by the parent compounds.A promising procedure applied to produce modifications of medicines at molecular level consists in exposing them in solutions at laser radiation that has particular characteristics in terms of wavelength, energy/power, time distribution of the emission (i.e. continuous wavecw or pulsed), pulse duration and repetition rates; according to the present knowledge, the polarization state of the beams and their time and spatial coherence do not have critical influence on the processes Comparative data were obtained on the evolution of neovascularisation of the conjunctive between untreated rabbit eyes and eyes impregnated with cytostatics at 5x10 -5 M in natural saline which are exposed to coherent or noncoherent light beams. The model simulates the tumor and the tests have shown that conjunctive and neovascularisations disappear after 1-2 treatments. 5-FU is a pyrimidine analog that belongs to the family of antimetabolites. It is weakly fluorescent, but it emits intense fluorescence after exposure to UV-VIS light. The UV-VIS absorption spectra of 5-FU did not show any structural modification after exposure to UV laser beams, but the FTIR spectra showed that the molecular geometry of 5-FU was changed after irradiation. The exposure to UV laser radiation transformed the 5-FU molecule into a tautomeric form. The increase of the fluorescence is attributed to a higher conversion to the keto-enol (lactim form) fluorescing tautomer due to monochromatic and high intensity laser radiation, which allows an effective and selective excitation. The radicals formed by the deprotonation of 5-FU could initiate the tumoricidal effect. The spectroscopic studies were coupled with preliminary tests on 5-FU photosensitizing properties measured on rabbit eyes conjunctive tissues [2]. Comparative data were obtained about the evolution of neovascularisations in the conjunctive tissue between untreated rabbit eyes and eyes impregnated with 5-FU 10 -4 M in natural saline and exposed to a UV-light beam emitted by a nitrogen pulsed l...

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confidence: 99%

The Laser Use in Generating New Species of Medicines with Antitumor and Antibacterial Properties: New Processes in Drug Discovery

Pascu¹

2012

Biochem & Pharmacol

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“…Of particular interest is that the irradiation process yields a product that has greater activity against the Gram-positive Staphylococcus aureus than the parental un-irradiated compound [37]. These preliminary studies supported the concept that exposure of a medicinal compound to a given laser beam of high energy could not only modify its structure, but could also yield one or more species that have greater biologic activity with perhaps a lesser degree of toxicity.…”

Section: Introductionmentioning

confidence: 68%

“…In order to insure that the irradiation of CPZ takes place at initial concentrations that do not lead to polymers formation, a polymerization test was performed as in [37] mentioning that in all the experiments no additives were added and only distilled water was used as a solvent. Concentrations as high as 20 mg/mL were shown to express a behavior that will not affect the absorbance spectrum of the control.…”

Section: Methodsmentioning

confidence: 99%

“…The disks were placed onto the agar plate containing the swabbed bacteria, the plates incubated overnight at 37°C and the zones of inhibition, if present, measured in mm. The MIC of CPZ and irradiated CPZ samples were conducted by the broth dilution method [37]. It is to mention that the solutions exposed to laser radiation contain not only the parent compound (if such a compound or at least a fraction of it remain in the solution) but also the long lived photoproducts which last in the solution.…”

Section: Methodsmentioning

confidence: 99%

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Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

et al. 2013

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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.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Morán

Tozar

Simon

et al. 2016

Colloids and Surfaces B: Biointerfaces

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Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions in water at 20mg/mL concentration to increase antibacterial activity of resulting mixtures. Compared to previous results obtained on bacteria, more research is needed about UV laser irradiated phenothiazines applications on cancer cell cultures to evidence possible anticancerous properties. Evaluation of the safety of the newly obtained photoproducts in view of use on humans is also needed. Due to expensive animal testing in toxicology and pressure from general public and governments to develop alternatives to in vivo testing, in vitro cell-based models are attractive for preliminary testing of new materials. Cytotoxicity screening reported here shows that laser irradiated (4h exposure time length) chlorpromazine and promazine are more efficient against some cell cultures. Interaction of laser irradiated phenothiazines with fabrics show that promethazine and chlorpromazine have improved wetting properties. Correlation of these two groups of properties shows that chlorpromazine appears to be more recommended for applications on tissues using fabrics as transport vectors. The reported results concern stability study of phenothiazines water solutions to know the time limits within which they are stable and may be used.

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Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation

Cited by 18 publications

References 16 publications

The Laser Use in Generating New Species of Medicines with Antitumor and Antibacterial Properties: New Processes in Drug Discovery

The Laser Use in Generating New Species of Medicines with Antitumor and Antibacterial Properties: New Processes in Drug Discovery

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

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

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