Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Chem ; 9: 707876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249874

RESUMO

Phototherapies, in the form of photodynamic therapy (PDT) and photothermal therapy (PTT), are very promising treatment modalities for cancer since they provide locality and turn-on mechanism for toxicity, both of which are critical in reducing off-site toxicity. Irradiation of photosensitive agents demonstrated successful therapeutic outcomes; however, each approach has its limitations and needs to be improved for clinical success. The combination of PTT and PDT may work in a synergistic way to overcome the limitations of each method and indeed improve the treatment efficacy. The development of single photosensitive agents capable of inducing both PDT and PTT is, therefore, extremely advantageous and highly desired. Cyanine dyes are shown to have such potential, hence have been very popular in the recent years. Luminescence of cyanine dyes renders them as phototheranostic molecules, reporting the localization of the photosensitive agent prior to irradiation to induce phototoxicity, hence allowing image-guided phototherapy. In this review, we mainly focus on the cyanine dye-based phototherapy of different cancer cells, concentrating on the advancements achieved in the last ten years.

2.
ACS Med Chem Lett ; 12(5): 752-757, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34055222

RESUMO

Iodination of the silicon-fluorescein core revealed a new class of highly cytotoxic, red-shifted and water-soluble photosensitizer (SF-I) which is also fairly emissive to serve as a theranostic agent. Singlet oxygen generation capacity of SF-I was evaluated chemically, and up to 45% singlet oxygen quantum yield was reported in aqueous solutions. SF-I was further tested in triple negative breast (MDA MB-231) and colon (HCT-116) cancer cell lines, which are known to have limited chemotherapy options as well as very poor prognosis. SF-I induced efficient singlet oxygen generation and consequent photocytotoxicity in both cell lines upon light irradiation with a negligible dark toxicity while allowing cell imaging at the same time. SF-I marks the first ever example of a silicon xanthene-based photosensitizer and holds a lot of promise as a small-molecule-based theranostic scaffold.

3.
J Photochem Photobiol B ; 217: 112171, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33711563

RESUMO

Dual phototherapy agents have attracted great interest in recent years as they offer enhanced cytotoxicity on cancer cells due to the synergistic effect of photodynamic and photothermal therapies (PDT/PTT). In this study, we demonstrate a brominated hemicyanine (HC-1), which is previously shown as mitochondria targeting PDT agent, can also serve as an effective photosensitizer for PTT for the first time under a single (640 nm or 808 nm) and dual laser (640 nm + 808 nm) irradiation. Generation of reactive oxygen species and photothermal conversion as a function of irradiation wavelength and power were studied. Both single wavelength irradiations caused significant phototoxicity in colon and cervical cancer cells after 5 min of irradiation. However, co-irradiation provided near-complete elimination of cancer cells due to synergistic action. This work introduces an easily accessible small molecule-based synergistic phototherapy agent, which holds a great promise towards the realization of local, rapid and highly efficient treatment modalities against cancer.


Assuntos
Apoptose/efeitos dos fármacos , Carbocianinas/farmacologia , Lasers , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos da radiação , Carbocianinas/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Citometria de Fluxo , Humanos , Neoplasias/patologia , Neoplasias/terapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo
4.
ACS Med Chem Lett ; 11(12): 2491-2496, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33335672

RESUMO

A red-absorbing, water-soluble, and iodinated resorufin derivative (R1) that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. R1 showed high 1O2 generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. R1 induced photocytotoxicity after being triggered by endogenous MAO enzyme in cancer cells with a much higher efficiency in SH-SY5Y neuroblastoma cells with high MAO-A expression. Additionally, R1 displayed differential cytotoxicity between cancer and normal cells, without any considerable dark toxicity. To the best of our knowledge, R1 marks the first example of a resorufin-based photosensitizer (PS) as well as the first anticancer drug that is activated by a MAO enzyme. Remarkably, the target PDT agent was obtained only in three steps as a result of versatile resorufin chemistry.

5.
ChemMedChem ; 14(22): 1879-1886, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31663667

RESUMO

Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher 1 O2 generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells. The selectivity is believed to arise from differences in mitochondrial membrane potentials of healthy and cancerous cells. To the best of our knowledge, this marks the first example of a MT-targeted BODIPY PS that functions under hypoxic conditions. Remarkably, thanks to the design strategy, all these properties where realized by a compound that was synthesized in only five steps with 32 % overall yield. Hence, this material holds great promise for the realization of next-generation PDT drugs for the treatment of hypoxic solid tumors.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Hipóxia Celular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Camundongos , Estrutura Molecular , Células NIH 3T3 , Compostos Organosselênicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Relação Estrutura-Atividade
6.
Chem Soc Rev ; 47(7): 2228-2248, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29493684

RESUMO

The field of molecular logic gates originated 25 years ago, when A. P. de Silva published a seminal article in Nature. Stimulated by this ground breaking research, scientists were inspired to join the race to simulate the workings of the fundamental components of integrated circuits using molecules. The rules of this game of mimicry were flexible, and have evolved and morphed over the years. This tutorial review takes a look back on and provides an overview of the birth and growth of the field of molecular logics. Spinning-off from chemosensor research, molecular logic gates quickly proved themselves to be more than intellectual exercises and are now poised for many potential practical applications. The ultimate goal of this vein of research became clearer only recently - to "boldly go where no silicon-based logic gate has gone before" and seek out a new deeper understanding of life inside tissues and cells.


Assuntos
Computadores Moleculares/tendências , Lógica , Humanos , Peróxido de Hidrogênio/análise , Mercúrio/análise , Estrutura Molecular , Imagem Óptica
7.
ACS Chem Biol ; 13(7): 1844-1852, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29112372

RESUMO

Copper is an essential nutrient for sustaining life, and emerging data have expanded the roles of this metal in biology from its canonical functions as a static enzyme cofactor to dynamic functions as a transition metal signal. At the same time, loosely bound, labile copper pools can trigger oxidative stress and damaging events that are detrimental if misregulated. The signal/stress dichotomy of copper motivates the development of new chemical tools to study its spatial and temporal distributions in native biological contexts such as living cells. Here, we report a family of fluorescent copper sensors built upon carbon-, silicon-, and phosphorus-substituted rhodol dyes that enable systematic tuning of excitation/emission colors from orange to near-infrared. These probes can detect changes in labile copper levels in living cells upon copper supplementation and/or depletion. We demonstrate the ability of the carbon-rhodol based congener, Copper Carbo Fluor 1 (CCF1), to identify elevations in labile copper pools in the Atp7a-/- fibroblast cell model of the genetic copper disorder Menkes disease. Moreover, we showcase the utility of the red-emitting phosphorus-rhodol based dye Copper Phosphorus Fluor 1 (CPF1) in dual-color, dual-analyte imaging experiments with the green-emitting calcium indicator Calcium Green-1 to enable simultaneous detection of fluctuations in copper and calcium pools in living cells. The results provide a starting point for advancing tools to study the contributions of copper to health and disease and for exploiting the rapidly growing palette of heteroatom-substituted xanthene dyes to rationally tune the optical properties of fluorescent indicators for other biologically important analytes.


Assuntos
Cobre/metabolismo , Corantes Fluorescentes/química , Compostos Heterocíclicos com 3 Anéis/química , Animais , Cor , Desenho de Fármacos , Fluorescência , Corantes Fluorescentes/síntese química , Células HEK293 , Compostos Heterocíclicos com 3 Anéis/síntese química , Humanos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Estrutura Molecular
8.
Angew Chem Int Ed Engl ; 55(11): 3606-10, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26845734

RESUMO

The photodynamic therapy of cancer is contingent upon the sustained generation of singlet oxygen in the tumor region. However, tumors of the most metastatic cancer types develop a region of severe hypoxia, which puts them beyond the reach of most therapeutic protocols. More troublesome, photodynamic action generates acute hypoxia as the process itself diminishes cellular oxygen reserves, which makes it a self-limiting method. Herein, we describe a new concept that could eventually lead to a change in the 100 year old paradigm of photodynamic therapy and potentially offer solutions to some of the lingering problems. When gold nanorods with tethered endoperoxides are irradiated at 808 nm, the endoperoxides undergo thermal cycloreversion, resulting in the generation of singlet oxygen. We demonstrate that the amount of singlet oxygen produced in this way is sufficient for triggering apoptosis in cell cultures.


Assuntos
Ouro/química , Nanotubos/química , Fotoquimioterapia , Oxigênio Singlete/metabolismo , Apoptose , Células HeLa , Humanos , Microscopia Eletrônica de Transmissão , Espécies Reativas de Oxigênio/metabolismo
9.
Isr J Chem ; 56(9-10): 724-737, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263315

RESUMO

Copper is an essential element in biological systems. Its potent redox activity renders it necessary for life, but at the same time, misregulation of its cellular pools can lead to oxidative stress implicated in aging and various disease states. Copper is commonly thought of as a static cofactor buried in protein active sites; however, evidence of a more loosely bound, labile pool of copper has emerged. To help identify and understand new roles for dynamic copper pools in biology, we have developed selective molecular imaging agents for this metal, drawing inspiration from both biological binding motifs and synthetic model complexes that reveal thioether coordination as a general design strategy for selective and sensitive copper recognition. In this review, we summarize some contributions, primarily from our own laboratory, on fluorescence- and magnetic resonance-based molecular-imaging probes for studying copper in living systems using thioether coordination chemistry.

10.
Angew Chem Int Ed Engl ; 54(18): 5340-4, 2015 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-25809556

RESUMO

The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O2 (a(1) Δg )], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer-related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH). The reaction alters the properties of both the ground and excited states, consequently enabling the efficient generation of singlet oxygen. Remarkably, the designed photosensitizer can discriminate between different concentrations of GSH in normal and cancer cells and thus remains inefficient as a photosensitizer inside a normal cell while being transformed into a lethal singlet oxygen source in cancer cells. This is the first demonstration of such a difference in the intracellular activity of a photosensitizer.


Assuntos
Apoptose , Corantes Fluorescentes/síntese química , Glutationa/metabolismo , Fármacos Fotossensibilizantes/síntese química , Porfobilinogênio/análogos & derivados , Oxigênio Singlete/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dimerização , Citometria de Fluxo , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Luz , Camundongos , Microscopia Confocal , Modelos Moleculares , Estrutura Molecular , Células NIH 3T3 , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfobilinogênio/síntese química , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Oxigênio Singlete/química
11.
Org Lett ; 16(12): 3260-3, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24885413

RESUMO

A selective probe for glutathione was designed and synthesized. The design incorporates spatial and photophysical constraints for the maximal emission signal. Thus, pHs, as well as the intracellular thiol concentrations, determine the emission signal intensity through a tight control of charge-transfer and PeT processes. The probe works satisfactorily inside the human breast adenocarcinoma cells, highlighting GSH distribution in the cytosol.


Assuntos
Corantes Fluorescentes/síntese química , Glutationa/análise , Neoplasias da Mama , Feminino , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Transdução de Sinais
12.
Org Lett ; 16(3): 660-3, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24417281

RESUMO

A dissymmetrically substituted orthogonal BODIPY dimer and an orthogonal BODIPY trimer exist as two stable conformers, which are in fact atropisomeric enantiomers. The racemic mixture can be separated by HPLC using a chiral stationary phase. These enantiomeric derivatives hold great potential as chiral agents in asymmetric synthesis, fluorogenic/chromogenic sensing, and biological applications.


Assuntos
Compostos de Boro/química , Compostos Cromogênicos/química , Corantes/química , Corantes Fluorescentes/química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Estereoisomerismo
13.
Org Lett ; 15(1): 216-9, 2013 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-23256788

RESUMO

Judicious design of BODIPY dyes carrying nitroethenyl substituents in conjugation with the BODIPY core yields dyes that respond to biological thiols by both absorbance and emission changes. Incorporation of solubilizing ethyleneglycol units ensures water solubility. The result is bright signaling of biologically relevant thiols in the longer wavelength region of the visible spectrum and in aqueous solutions.


Assuntos
Compostos de Boro/síntese química , Corantes Fluorescentes/síntese química , Compostos de Sulfidrila/análise , Compostos de Boro/química , Corantes Fluorescentes/química , Indicadores e Reagentes , Estrutura Molecular , Soluções , Água/química
14.
J Org Chem ; 77(10): 4516-27, 2012 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-22530939

RESUMO

S(0), S(1), and T(1) states of various orthogonal 8,8' and 8,2'-bis-boradiaza-s-indacene (BODIPY) dyes, recently (Angew. Chem., Int. Ed.2011, 50, 11937) proposed as heavy atom free photosensitizers for O(2)((1)Δ(g)) generation, were studied by multireference quantum chemical approaches. S(0)→S(1) excitation characteristics of certain bis-BODIPYs are shown to be drastically different than the parent BODIPY chromophore. Whereas a simple HOMO→LUMO-type single substitution perfectly accounts for the BODIPY core, S(1) states of certain orthogonal bis-BODIPYs are described as linear combinations of doubly substituted (DS) configurations which overall yield four electrons in four singly occupied orbitals. Computed DS character of S(1), strongly correlated with facile (1)O(2) production, was presumed to occur via S(1)→T(1) intersystem crossing (ISC) of the sensitizer. Further confirmation of this relation was provided by newly synthesized BODIPY derivatives and comparison of spectroscopic properties of their dimers and monomers. Near-IR absorption, desired for potential photodynamic therapy applications, was not pursuable for bis-chromophores by the standard strategy of π-extension, as DS singlet states are destabilized. Decreased exchange coupling in π-extended cases appears to be responsible for this destabilization. Comparisons with iodine incorporated bis-BODIPYs suggest that the dynamics of (1)O(2) generation via DS S(1) states are qualitatively different from that via ISC originating from heavy atom spin-orbit coupling. Although red-shifting the absorption wavelength to enter the therapeutic window does not seem attainable for orthogonal bis-BODIPYs with DS S(1) states, modifications in the chromophore cores are shown to be promising in fine-tuning the excitation characteristics.

16.
Org Lett ; 12(17): 3812-5, 2010 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-20704314

RESUMO

Boron-dipyrrin dyes, through rational design, yield promising new materials. With strong electron-donor functionalities and anchoring groups for attachment to nanocrystalline TiO(2), these dyes proved useful as sensitizers in dye-sensitized solar cells. Their applicability in a solid-state electrolyte regime offers additional opportunities for practical applications.

17.
J Am Chem Soc ; 132(23): 8029-36, 2010 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-20297820

RESUMO

Remarkably versatile chemistry of Bodipy dyes allows the design and straightforward synthesis of multivalent-multitopic derivatives, which, with judicious selection of metal ion-ligand pairs based on known affinities, affords control and manipulation of photoinduced electron transfer and internal charge transfer processes as desired. We have demonstrated that metal ions acting as modulators (or inputs, in digital design parlance) can generate absorbance changes in accordance with the operation of a half-adder. In addition, an AND logic gate in the emission mode was delivered using a different binucleating arrangement of ligands. A molecular equivalent of a three-input AND logic gate was also obtained exploiting differential binding affinities of metal ions for different ligands. The results suggest that different metal ions can be used as nonannihilating inputs, selectively targeting various ligands incorporated within a single fluorophore, and with careful design, diverse photophysical processes can be selectively modulated, resulting in a range of signals, useful in molecular logic design, and offering an enticing potential for multianalyte chemosensors.

18.
Org Lett ; 11(20): 4644-7, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-19757825

RESUMO

1,3,5,7-Tetramethyl-Bodipy derivatives undergo Knoevenagel-type condensations with aromatic aldehydes to ultimately yield tetrastyryl-Bodipy derivatives. The resulting dyes absorb and emit strongly in the near IR. As the versatility of the Bodipy dyes are fully appreciated, these new tetrastyryl dyes are likely to be featured in a variety of functional supramolecular systems.


Assuntos
Compostos de Boro/química , Compostos de Boro/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Raios Infravermelhos , Absorção , Aldeídos/química , Espectroscopia de Ressonância Magnética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...