Photochemical Reactions of Chlorpromazine; Chemical and Biochemical Implications

Rosenthal, I.; Ben‐Hur, E.; Prager, A.; Riklis, E.

doi:10.1111/j.1751-1097.1978.tb06975.x

Cited by 62 publications

(27 citation statements)

References 13 publications

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“…According to Rosenthal et al . (16) and Davis et al. (5), the sulfoxide can also be produced by the attack of singlet oxygen to the ground state of CPZ.…”

Section: Introductionmentioning

confidence: 97%

Photodegradation of 2‐chloro Substituted Phenothiazines in Alcohols

García

Piñero

Oyola

et al. 2009

Photochem & Photobiology

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The mechanisms that trigger the phototoxic response to 2-chlorophenothiazine derivatives are still unknown. To better understand the relationship between the molecular structure of halogenated phenothiazines and their phototoxic activity, their photophysics and photochemistry were studied in several alcohols. The photodestruction quantum yields were determined under anaerobic conditions using monochromatic light (313 nm). Absorption-and emission-spectroscopy, 1 H-and 13 C-NMR and GC-MS were used to characterize the photoproducts and reference compounds. An electron transfer mechanism had been previously proposed by Bunce et al. (J. Med. Chem. 22,[202][203][204] to explain the large difference between the photodestruction quantum yield of 2-chlorpromazine (u = 0.46) and 2-chlorphenothiazine (u = 0.20). According to these authors, the alkylamino chain transfers an electron to the phenothiazine moiety. Our results demonstrate that this mechanism is incorrect, because the photodestruction quantum yields of all chlorinated derivatives of this study are the same under the same conditions of solvent and irradiation wavelength. The quantum yield has no dependence on the 10-substituent, but it depends on the solvent. The percentage of each photoproduct, on the other hand, strongly depends on that substituent, but not very much on the solvent. Finally, it is demonstrated that the phototoxic effect of chlorinated phenothiazines is not related to the photodechlorination, although both processes share the same transient.

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“…According to Rosenthal et al . (16) and Davis et al. (5), the sulfoxide can also be produced by the attack of singlet oxygen to the ground state of CPZ.…”

Section: Introductionmentioning

confidence: 97%

Photodegradation of 2‐chloro Substituted Phenothiazines in Alcohols

García

Piñero

Oyola

et al. 2009

Photochem & Photobiology

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“…The nucleophilic photosubstitution was confirmed by reaction in alcohols. Rosenthal et al [43] irradiated CPZ hydrochloride solutions in methanol with wavelengths greater than 300 nm in the absence of oxygen. They identified PMZ and 2-methoxyPMZ.…”

Section: Photochemistry Of Phenothiazinesmentioning

confidence: 99%

“…Photobinding of CPZ has been demonstrated on proteins in solution such as bovine and human serum albumin [126,150]. The photobinding to protein of various phenothiazine derivatives (CPZ, FPZ, PMZ and PMTZ) has been studied on four different types of biological membranes such as microsomes, myelin and synaptosome from rat brain as well as human erythrocytes [151].…”

Section: Proteins and Lipids Photodamage By Pheno-thiazine Derivativementioning

confidence: 99%

Photosensitization of Biomolecules by Phenothiazine Derivatives

Viola¹,

Dall’Acqua

2006

CDT

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It is well known that many drugs act as photosensitizers towards cells by interacting with various cellular components such as lipids, proteins and nucleic acids. The structural modifications of the cellular components may occur by direct interactions of the excited states (singlets or triplets) of the drugs with the biological substrate or indirectly, through reactive species of oxygen sensitised by the drug themselves. In particular, the phototoxic activity of various drugs correlated with their potential photomutagenic and photocarcinogenic effects, takes place through DNA modification. Phenothiazines, a class of antihistaminic (anti-H1) or neuroleptic drugs used in the therapy of mental illness, such as schizophrenia, organic psychoses and other mental disorders, are known to induce photosensitization of the skin by systemic use or by topical applications as antiallergic drugs. In this review we have focused our attention on the photosensitizing property of phenothiazines and related compounds both in vitro and in vivo systems. Particular attention has been given to the mechanism of photo reaction with biomolecules such as lipids, proteins and DNA. Moreover there is a growing interest in drugs having photobiological effects because of their possible application as phototherapeutics. It has been interesting in this context to mention briefly the possible application of phenothiazine derivatives as new photosensitizers for their therapeutic application in photodynamic therapy (PDT) or in the light inactivation of viruses and bacteria.

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“…40 Attempts to inactivate scrapie prions with nucleases, ultraviolet irradiation at 254 nm, Zn2+ catalyzed hydrolysis, psoralen photoinactivation and chemical modification by hydroxylamine have all been 413 4 2 even using preparations which contain one major protein as determined by amino acid sequencing (C. G. Bellinger-Kawahara, J. E. Cleaver, T. 0. Diener and S .…”

Section: Search For a Prion Genome Continuesmentioning

confidence: 99%

Prions are novel infectious pathogens causing scrapie and creutzfeldt—Jakob disease

Prusiner

1986

BioEssays

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SummaryScrapie and Creutzfeldt-Jakob disease (CJD) are caused by prions, which appear to be different from both viruses and viroids. Prions contain protein which is required for infectivity, but no nucleic acid has been found within them. Prion proteins are encoded by a cellular gene and not by a nucleic acid within the infectious prion particle. A cellular homologue of the prion protein has been identijied. The role of this homologue in metabolism is unknown. Prion proteins, but not the cellular homologue, aggregate into rod-shaped particles that are histochemically and ultrastructurally identical to amyloid. Extracellular collections of prion proteins form amyloid plaques in scrapie-and CJD-infected rodent brains as well as CJD-infected human brains. Within the plaques, prion proteins assemble to form amyloidJlaments. Elucidating the molecular dtgerences between the prion protein and its cellular homorogue may be important in understanding the chemical structure and replication of prions. Animal and Human Prion DiseasesIn developing models for the study of degenerative neurologic diseases, we have focused our attention on the study of scrapie, a degenerative neurologic disorder of sheep and goats. Scrapie occurs after a prolonged incubation period and is readily transmissible to laboratory rodents. The disease is characterized by progressive neurologic dysfunction caused by degeneration of the C.N.S. Neuropathologic changes include proliferation of glial cells, vacuolation of neurons and depositions of extracellular amyloid in the form of plaques.

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Photochemical Reactions of Chlorpromazine; Chemical and Biochemical Implications

Cited by 62 publications

References 13 publications

Photodegradation of 2‐chloro Substituted Phenothiazines in Alcohols

Photodegradation of 2‐chloro Substituted Phenothiazines in Alcohols

Photosensitization of Biomolecules by Phenothiazine Derivatives

Prions are novel infectious pathogens causing scrapie and creutzfeldt—Jakob disease

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