Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Eur J Med Chem ; 183: 111683, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31514060

ABSTRACT

While photodynamic therapy is known for significant advantages over conventional cancer therapies, its dependence on light has limited it to treating tumors on or just under the skin or on the outer lining of organs/cavities. Herein, we have developed a single-molecule photosensitizer capable of intracellular self-activation and with potential tumor-selectivity due to a chemiluminescent reaction involving only a cancer marker. Thus, the photosensitizer is directly chemiexcited to a triplet excited state capable of generating singlet oxygen, without requiring either a light source or any catalyst/co-factor. Cytotoxicity assays involving the photosensitizer show significant toxicity toward tumor cells, even better than reference drugs, while not inducing toxicity toward normal cells. This work provides a proof-of-concept for a novel type of photosensitizer that eliminates the current restrictions that photodynamic therapy presents regarding tumor size and localization.


Subject(s)
Imidazoles/chemistry , Neoplasms/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Pyrazines/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Computer Simulation , Humans , Light , Photosensitizing Agents/pharmacology , Proof of Concept Study , Pyrazines/pharmacology , Singlet Oxygen/metabolism , Thermodynamics
2.
Biomolecules ; 9(8)2019 08 20.
Article in English | MEDLINE | ID: mdl-31434290

ABSTRACT

Cancer is a very challenging disease to treat, both in terms of treatment efficiency and side-effects. To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Analysis of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable.


Subject(s)
Antineoplastic Agents/pharmacology , Imidazoles/pharmacology , Photochemotherapy , Photosensitizing Agents/pharmacology , Pyrazines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Imidazoles/chemical synthesis , Imidazoles/chemistry , MCF-7 Cells , Molecular Structure , PC-3 Cells , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Pyrazines/chemical synthesis , Pyrazines/chemistry , Tumor Cells, Cultured
3.
J Photochem Photobiol B ; 174: 18-26, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28750319

ABSTRACT

Coelenterazine is a widespread bioluminescent substrate for a diverse set of marine species. Moreover, its imidazopyrazinone core is present in eight phyla of bioluminescent organisms. Given their very attractive intrinsic properties, these bioluminescent systems have been used in bioimaging, photodynamic therapy of cancer, as gene reporter and in sensing applications, among others. While it is known that bioluminescence results from the thermolysis of high-energy dioxetanones, the mechanism and dioxetanone species responsible for the singlet chemiexcitation of Coelenterazine are not fully understood. The theoretical characterization of the reactions of model Coelenterazine dioxetanones showed that efficient chemiexcitation is caused by a neutral dioxetanone with limited electron and charge transfer, by accessing a region of the PES where ground and excited states are nearly-degenerated. This finding was supported by calculation of equilibrium constants, which showed that only neutral dioxetanone is present in conditions associated with bioluminescence. Moreover, while cationic amino-acids easily protonate amide dioxetanone, anionic ones cannot deprotonate the neutral species. These results indicate that, contrary to existent theories, efficient chemiexcitation can occur with significant electron and/or charge transfer. In fact, these processes can be prejudicial to chemiexcitation, as anionic dioxetanones showed a less efficient chemiexcitation despite the occurrence of significant electron and charge transfer.


Subject(s)
Heterocyclic Compounds, 1-Ring/chemistry , Imidazoles/chemistry , Models, Chemical , Pyrazines/chemistry , Amides/chemistry , Electron Transport , Luminescence , Models, Molecular , Molecular Conformation
4.
Photochem Photobiol Sci ; 14(2): 465-72, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25521601

ABSTRACT

In this study, a theoretical approach was used to study the UV absorption of the UVB filter, 4-methylbenzylidene camphor. The main objective of this work was to design new UVA filters based on this rather photo-stable compound, so that photo-degradation in this UV region can be avoided without the use of other molecules. This objective was achieved by the simultaneous addition of two appropriate substituents, which led to red-shifts of up to 0.69 eV while maintaining appreciable oscillator strength. Also, useful structure-energy relationships were derived, which allow for the development of more UVA filters based on 4-methylbenzylidene camphor.

5.
J Phys Chem A ; 118(8): 1511-8, 2014 Feb 27.
Article in English | MEDLINE | ID: mdl-24494821

ABSTRACT

The growing awareness of the harmful effects of ultraviolet (UV) solar radiation has increased the production and consumption of sunscreen products, which contain organic and inorganic molecules named UV filters that absorb, reflect, or scatter UV radiation, thus minimizing negative human health effects. 4-tert-Butyl-4'-methoxydibenzoylmethane (BMDBM) is one of the few organic UVA filters and the most commonly used. BMDBM exists in sunscreens in the enol form which absorbs strongly in the UVA range. However, under sunlight irradiation tautomerization occurs to the keto form, resulting in the loss of UV protection. In this study we have performed quantum chemical calculations to study the excited-state molecular structure and excitation spectra of the enol and keto tautomers of BMDBM. This knowledge is of the utmost importance as the starting point for studies aiming at the understanding of its activity when applied on human skin and also its fate once released into the aquatic environment. The efficiency of excitation transitions was rationalized based on the concept of molecular orbital superposition. The loss of UV protection was attributed to the enol → keto phototautomerism and subsequent photodegradation. Although this process is not energetically favorable in the singlet bright state, photodegradation is possible because of intersystem crossing to the first two triplet states.


Subject(s)
Alkanes/chemistry , Chalcones/chemistry , Sunscreening Agents/chemistry , Alkanes/radiation effects , Chalcones/radiation effects , Isomerism , Molecular Structure , Photolysis , Propiophenones , Quantum Theory , Spectrum Analysis/methods , Sunscreening Agents/radiation effects , Thermodynamics , Ultraviolet Rays
SELECTION OF CITATIONS
SEARCH DETAIL
...