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The survival fraction of epithelial HaCaT cells was analysed to assess the biological damage caused by intraoperative radiotherapy electron beams with varying energy spectra and intensities. These conditions were achieved by irradiating the cells at different depths in water using nominal 6 MeV electron beams while consistently delivering a dose of 5 Gy to the cell layer. Furthermore, a Monte Carlo simulation of the entire irradiation procedure was performed to evaluate the molecular damage in terms of molecular dissociations induced by the radiation. A significant agreement was found between the molecular damage predicted by the simulation and the damage derived from the analysis of the survival fraction. In both cases, a linear relationship was evident, indicating a clear tendency for increased damage as the averaged incident electron energy and intensity decreased for a constant absorbed dose, lowering the dose rate. This trend suggests that the radiation may have a more pronounced impact on surrounding healthy tissues than initially anticipated. However, it is crucial to conduct additional experiments with different target geometries to confirm this tendency and quantify the extent of this effect.
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Células Epiteliais , Radioterapia de Alta Energia , Células HaCaT , Sobrevivência Celular , Elétrons , Humanos , Método de Monte Carlo , Radioterapia de Alta Energia/efeitos adversos , Células Epiteliais/efeitos da radiação , Relação Dose-Resposta à RadiaçãoRESUMO
Solvent effects on the UV-vis spectra of 3-hydroxyflavone and other structurally related molecules (3-hydroxychromen-4-one, 3-hydroxy-4-pyrone, and 4-pyrone) have been studied by combining time-dependent density functional theory (TDDFT) and the polarizable continuum method (PCM). Among the first five excited states of the four considered molecules, electronic states of n â π* and π â π* nature appear. In general, the stability of the n â π* states decreases as the π space becomes larger in such a way that only for 4-pyrone and 3-hydroxy-4-pyrone are they the first excited states. In addition, they become less stabilized in ethanol solution than the ground state, and this causes blueshift transitions in solution. The opposite trend is found for the π â π* excited states. They are less energetic with the π-system size and when passing from gas phase to solution. The solvent shift also depends strongly on the size of the π systems and on the formation of an intramolecular hydrogen bond; thus, it decreases when going from 4-pyrone to 3-hydroxyflavone. The performance of the three versions (cLR, cLR2, and IBSF) of the specific-state PCM method in predicting transition energies are compared.
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Lung cancer is the leading cause of cancer-related death worldwide. Its late diagnosis and consequently poor survival make necessary the search for new therapeutic targets. The mitogen-activated protein kinase (MAPK)-interacting kinase 1 (MNK1) is overexpressed in lung cancer and correlates with poor overall survival in non-small cell lung cancer (NSCLC) patients. The previously identified and optimized aptamer from our laboratory against MNK1, apMNKQ2, showed promising results as an antitumor drug in breast cancer in vitro and in vivo. Thus, the present study shows the antitumor potential of apMNKQ2 in another type of cancer where MNK1 plays a significant role, such as NSCLC. The effect of apMNKQ2 in lung cancer was studied with viability, toxicity, clonogenic, migration, invasion, and in vivo efficacy assays. Our results show that apMNKQ2 arrests the cell cycle and reduces viability, colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT) processes in NSCLC cells. In addition, apMNKQ2 reduces tumor growth in an A549-cell line NSCLC xenograft model. In summary, targeting MNK1 with a specific aptamer may provide an innovative strategy for lung cancer treatment.
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Aptamers are single-stranded oligonucleotides able to recognize a target with high affinity and specificity. Aptamers are used in different diagnostics applications, highlighting, among all, variations of the traditional enzyme-linked immunosorbent assay (ELISA). In this chapter, we show the procedures for the development of two types of indirect ELONA: a sandwich ELONA and a direct ELONA coupled to either real-time quantitative PCR as a direct and sensitive readout.
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Aptâmeros de Nucleotídeos , Ensaios Enzimáticos , Ensaio de Imunoadsorção Enzimática , Reação em Cadeia da Polimerase em Tempo Real , Técnica de Seleção de Aptâmeros/métodosRESUMO
In this study, single-stranded DNA aptamers with binding affinity to Ole e 1, the major allergen of olive pollen, were selected using systematic evolution of ligands by exponential enrichment (SELEX) method. Binding of the aptamers was firstly established by enzyme-linked oligonucleotide assay (ELONA) and aptaprecipitation assays. Additionally, aptamer-modified monolithic capillary chromatography was used in order to evaluate the recognition of this allergenic protein against other non-target proteins. The results indicated that AptOle1#6 was the aptamer that provided the highest affinity for Ole e 1. The selected aptamer showed good selective recognition of this protein, being not able to retain other non-target proteins (HSA, cyt c, and other pollen protein such as Ole e 9). The feasibility of the affinity monolithic column was demonstrated by selective recognition of Ole e 1 in an allergy skin test. The stability and reproducibility of this monolithic column was suitable, with relative standard deviations (RSDs) in retention times and peak area values of 7.8 and 9.3%, respectively (column-to-column reproducibility). This is the first study that describes the design of an efficient DNA aptamer for this relevant allergen.
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Aptâmeros de Nucleotídeos , Olea , Alérgenos , Pólen , Reprodutibilidade dos TestesRESUMO
Lung cancer is one of the leading causes of death worldwide and the most common of all cancer types. Histone acetyltransferase 1 (HAT1) has attracted increasing interest as a potential therapeutic target due to its involvement in multiple pathologies, including cancer. Aptamers are single-stranded RNA or DNA molecules whose three-dimensional structure allows them to bind to a target molecule with high specificity and affinity, thus making them exceptional candidates for use as diagnostic or therapeutic tools. In this work, aptamers against HAT1 were obtained, subsequently characterized, and optimized, showing high affinity and specificity for HAT1 and the ability to inhibit acetyltransferase activity in vitro. Of those tested, the apHAT610 aptamer reduced cell viability, induced apoptosis and cell cycle arrest, and inhibited colony formation in lung cancer cell lines. All these results indicate that the apHAT610 aptamer is a potential drug for the treatment of lung cancer.
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Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and its correlation with poor prognosis has been determined, showing VRK1 as a new therapeutic target in oncology. Using in vitro selection, high-affinity DNA aptamers to VRK1 were selected from a library of ssDNA. Selection was monitored using the enzyme-linked oligonucleotide assay (ELONA), and the selected aptamer population was cloned and sequenced. Three aptamers were selected and characterized. These aptamers recognized the protein kinase VRK1 with an affinity in the nanomolar range and showed a high sensibility. Moreover, the treatment of the MCF7 breast cell line with these aptamers resulted in a decrease in cyclin D1 levels, and an inhibition of cell cycle progression by G1 phase arrest, which induced apoptosis in cells. These results suggest that these aptamers are specific inhibitors of VRK1 that might be developed as potential drugs for the treatment of cancer.
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Environmental factors such as air pollution by particles and/or electromagnetic fields (EMFs) are studied as harmful agents for human health. We analyzed whether the combined action of EMF with fine and coarse black carbon (BC) particles induced cell damage and inflammatory response in RAW 264.7 cell line macrophages exposed to 2.45 GHz in a gigahertz transverse electromagnetic (GTEM) chamber at sub-thermal specific absorption rate (SAR) levels. Radiofrequency (RF) dramatically increased BC-induced toxicity at high doses in the first 24 h and toxicity levels remained high 72 h later for all doses. The increase in macrophage phagocytosis induced after 24 h of RF and the high nitrite levels obtained by stimulation with lipopolysaccharide (LPS) endotoxin 24 and 72 h after radiation exposure suggests a prolongation of the innate and inflammatory immune response. The increase of proinflammatory cytokines tumor necrosis factor-α, after 24 h, and of interleukin-1ß and caspase-3, after 72 h, indicated activation of the pro-inflammatory response and the apoptosis pathways through the combined effect of radiation and BC. Our results indicate that the interaction of BC and RF modifies macrophage immune response, activates apoptosis, and accelerates cell toxicity, by which it can activate the induction of hypersensitivity reactions and autoimmune disorders.
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Campos Eletromagnéticos , Ondas de Rádio , Animais , Carbono , Humanos , Macrófagos , Camundongos , Células RAW 264.7 , Ondas de Rádio/efeitos adversosRESUMO
In this work, the application of a technique for monitoring changes of the dielectric constant of the atmosphere caused by the presence of pollution is discussed. The method is based on changes in the reflection coefficient of the device induced by these dielectric constant variations of the surrounding medium. To that end, several Yagi-Uda-like antenna designs with different size limitations were simulated by using a Method-of-Moments software and optimized by means of a simulated annealing strategy. It has been found that the larger the optimal elements of the array are allowed to be, the higher the sensitivity reached. Thus, in a trade-off between sensitivity and moderate length (regarding flexibility purposes), the most promising solution has been built. This prototype has been experimentally tested in presence of an artificial aerosol made of PAO (polyalphaolefin) oil and black carbon inclusions of a size of 0.2 µm. As a result, potentials for developing a measurement procedure by means of changes in the characteristic parameters of the antenna led by different concentration levels of suspended particles in the surrounding medium are shown. In this manner, a local mapping of polluted levels could be developed in an easy, real-time, and flexible procedure.
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Leishmania infantum parasites cause a severe form of visceral leishmaniasis in human and viscerocutaneous leishmaniasis in dogs. Recently, we reported that immunization with an attenuated L. infantum cell line, lacking the hsp70-II gene, protects against the development of murine cutaneous leishmaniasis. In this work, we analyzed the vaccine potential of this cell line towards the long-term protection against murine visceral leishmaniasis. This model shows an organ-dependent evolution of the disease. The infection can resolve in the liver but chronically affect spleen and bone marrow. Twelve weeks after subcutaneous administration of attenuated L. infantum, Bagg Albino (BALB/c) mice were challenged with infective L. infantum parasites expressing the luciferase-encoding gene. Combining in vivo bioimaging techniques with limiting dilution experiments, we report that, in the initial phase of the disease, vaccinated animals presented lower parasite loads than unvaccinated animals. A reduction of the severity of liver damage was also detected. Protection was associated with the induction of rapid parasite-specific IFN-γ production by CD4+ and CD8+ T cells. However, the vaccine was unable to control the chronic phase of the disease, since we did not find differences in the parasite burdens nor in the immune response at that time point.
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Leishmaniasis is a disease caused by a parasite of the genus Leishmania that affects millions of people worldwide. These parasites are characterized by the presence of a DNA-containing granule, the kinetoplastid, located in the single mitochondrion at the base of the cell's flagellum. Interestingly, these flagellates do not condense chromatin during mitosis, possibly due to the specific molecular features of their histones. Although histones are extremely conserved proteins, kinetoplastid core histone sequences diverge significantly from those of higher eukaryotes. This divergence makes kinetoplastid core histones potential diagnostic and/or therapeutic targets. Aptamers are short single-stranded nucleic acids that are able to recognize target molecules with high affinity and specificity. Their binding capacity is a consequence of the particular three-dimensional structure acquired depending on their sequence. These molecules are currently used for detection, diagnosis and therapeutic purpose. Starting from a previously obtained ssDNA aptamer population against rLiH3 protein we have isolated two individual aptamers, AptLiH3#4 and AptLiH3#10. Next, we have performed ELONA, Western blot and slot blot assays to establish aptamer specificity and affinity for LiH3 histone. In addition, ELONA assays using peptides corresponding to overlapped sequences of LiH3 were made to map the aptamers:LiH3 interaction. Finally, different assays using aptamers were performed in order to evaluate the possibility of using these aptamers as sensing molecule to recognize the endogenous protein LiH3. Our results indicate that both aptamers have high affinity and specificity for the target and are able to detect the endogenous LiH3 histone protein in promastigotes lysates. In silico analysis reveals that these two aptamers have different potential secondary structure among them, however, both of them are able to recognize the same peptide sequences present in the protein. In conclusion, our findings indicate that these aptamers could be used for LiH3 histone detection and, in consequence, as potential biosensing molecules in a diagnostic tool for leishmaniasis.
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Aptâmeros de Nucleotídeos/química , DNA/química , Histonas/análise , Leishmania infantum/química , Proteínas de Protozoários/análise , Sequência de Aminoácidos , Aptâmeros de Nucleotídeos/metabolismo , Sequência de Bases , Técnicas Biossensoriais/métodos , DNA/metabolismo , Histonas/metabolismo , Limite de Detecção , Ligação Proteica , Proteínas de Protozoários/metabolismoRESUMO
A molecular motor potentially performing a continuous unidirectional rotation is studied by a multidisciplinary approach including organic synthesis, transient spectroscopy and excited state trajectory calculations. A stereogenic center was introduced in the N-alkylated indanylidene-pyrroline Schiff base framework of a previously investigated light-driven molecular switch in order to achieve the unidirectional C[double bond, length as m-dash]C rotary motion typical of Feringa's motor. Here we report that the specific substitution pattern of the designed chiral molecule must critically determine the unidirectional efficiency of the light-induced rotary motion. More specifically, we find that a stereogenic center containing a methyl group and a hydrogen atom as substituents does not create a differential steric effect large enough to fully direct the motion in either the clockwise or counterclockwise direction especially along the EâZ coordinate. However, due to the documented ultrafast character and electronic circular dichroism activity of the investigated system, we find that it provides the basis for development of a novel generation of rotary motors with a biomimetic framework and operating on a picosecond time scale.
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Adjuvant chemotherapy for solid tumors based on platinum-derived compounds such as cisplatin is the treatment of choice in most cases. Cisplatin triggers signaling pathways that lead to cell death, but it also induces changes in tumor cells that modify the therapeutic response, thereby leading to cisplatin resistance. We have recently reported that microRNA-7 is silenced by DNA methylation and is involved in the resistance to platinum in cancer cells through the action of the musculoaponeurotic fibrosarcoma oncogene family, protein G (MAFG). In the present study, we first confirm the miR-7 epigenetic regulation of MAFG in 44 normal- and/or tumor-paired samples in non-small-cell lung cancer (NSCLC). We also provide translational evidence of the role of MAFG and the clinical outcome in NSCLC by the interrogation of two extensive in silico databases of 2019 patients. Moreover, we propose that MAFG-mediated resistance could be conferred due to lower reactive oxygen species production after cisplatin exposure. We developed specifically selected aptamers against MAFG, with high sensitivity to detect the protein at a nuclear level probed by aptacytochemistry and histochemistry analyses. The inhibition of MAFG activity through the action of the specific aptamer apMAFG6F increased the levels of reactive oxygen species production and the sensitivity to cisplatin. We report first the specific nuclear identification of MAFG as a novel detection method for diagnosis in NSCLC, and then we report that MAFG modulates the redox response and confers cell protection against free radicals generated after platinum administration, thus also being a promising therapeutic target.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Fator de Transcrição MafG/antagonistas & inibidores , Proteínas Repressoras/antagonistas & inibidores , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Clonagem Molecular , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/fisiologia , Epigênese Genética/genética , Expressão Gênica , Inativação Gênica , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Fator de Transcrição MafG/genética , Fator de Transcrição MafG/fisiologia , MicroRNAs/genética , MicroRNAs/fisiologia , Oxirredução , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Análise de Sequência de DNA , TransfecçãoRESUMO
Since Toll-like receptor 4 (TLR4) mediates brain damage after stroke, development of TLR4 antagonists is a promising therapeutic strategy for this disease. Our aim was to generate TLR4-blocking DNA aptamers to be used for stroke treatment. From a random oligonucleotide pool, we identified two aptamers (ApTLR#1R, ApTLR#4F) with high affinity for human TLR4 by systematic evolution of ligands by exponential enrichment (SELEX). Optimized truncated forms (ApTLR#1RT, ApTLR#4FT) were obtained. Our data demonstrate specific binding of both aptamers to human TLR4 as well as a TLR4 antagonistic effect. ApTLR#4F and ApTLR#4FT showed a long-lasting protective effect against brain injury induced by middle cerebral artery occlusion (MCAO), an effect that was absent in TLR4-deficient mice. Similar effects were obtained in other MCAO models, including in rat. Additionally, efficacy of ApTLR#4FT in a model of brain ischemia-reperfusion in rat supports the use of this aptamer in patients undergoing artery recanalization induced by pharmacological or mechanical interventions. The absence of major toxicology aspects and the good safety profile of the aptamers further encourage their future clinical positioning for stroke therapy and possibly other diseases in which TLR4 plays a deleterious role.
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Aptâmeros de Nucleotídeos/administração & dosagem , Infarto da Artéria Cerebral Média/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Receptor 4 Toll-Like/metabolismo , Animais , Aptâmeros de Nucleotídeos/farmacologia , Modelos Animais de Doenças , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/etiologia , Camundongos , Ratos , Técnica de Seleção de Aptâmeros , Transdução de Sinais , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/metabolismoRESUMO
The chemokine (C-C motif) ligand 21 (CCL21) is a cytokine that attracts CCR7-positive cells to the T cell (paracortical) zone of lymph nodes by directional migration of these cells along the CCL21 gradient. In this article, we sought to mimic this chemotactic mechanism, by identifying a novel aptamer that binds CCL21 with high affinity. In vitro selection of DNA aptamers was performed by the Systematic Evolution of Ligands by Exponential Enrichment. Quantitative polymerase chain reaction (qPCR) and enzyme-linked oligonucleotide assay were used to screen for high-affinity aptamers against human and mouse CCL21 protein, respectively. Three such aptamers were identified. Surface plasmon resonance showed equilibrium dissociation constant (Kd) for these three aptamers in the nano to picomolar range. Cytotoxicity assays showed <10% toxicity in HEK293 and HL-60 cells. Last, in vivo biodistribution was successfully performed and CCL21 chemokine-binding aptamers were quantified within the draining lymph nodes and spleen using qPCR. Fluorescence microscopy revealed that one of the aptamers showed significantly higher presence in the paracortex than the control aptamer. The use of anti-CCL21 aptamers to mimic the chemotaxis mechanism thus represents a promising approach to achieve targeted delivery of drugs to the T cell-rich zones of the lymph node. This may be important for the treatment of HIV infection and the eradication of HIV reservoirs.
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Aptâmeros de Nucleotídeos/uso terapêutico , Quimiocina CCL21/genética , Infecções por HIV/prevenção & controle , Linfócitos T/efeitos dos fármacos , Animais , Movimento Celular , Quimiocina CCL21/antagonistas & inibidores , Sistemas de Liberação de Medicamentos , Células HEK293 , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Ligantes , Linfonodos/efeitos dos fármacos , Linfonodos/virologia , Camundongos , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania. Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, ß, and γ subunits and the α, ß, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2) or F2B (LieIF2B), respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum. In L. infantum (BALB/c) and Leishmania major (BALB/c or C57BL/6) challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bß and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the production of the down-regulatory IL-10 cytokine, favoring a pathological outcome. Therefore, these proteins might be considered markers of disease.
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Antígenos de Bactérias/imunologia , Fator de Iniciação 2B em Eucariotos/imunologia , Fator de Iniciação 2 em Eucariotos/imunologia , Leishmania infantum/imunologia , Leishmaniose/imunologia , Animais , Linfócitos B/imunologia , Biomarcadores , Cricetinae , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2B em Eucariotos/genética , Feminino , Interferon gama/metabolismo , Interleucina-10/metabolismo , Leishmania infantum/patogenicidade , Leishmaniose/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vacinas de DNA/imunologiaRESUMO
MAP kinase interacting kinases (MNKs) modulate the function of oncogene eukaryotic initiation factor 4E (eIF4E) through phosphorylation, which is necessary for oncogenic transformation. MNK1 gives rise to two mRNAs and thus two MNK1 isoforms, named MNK1a and MNK1b. MNK1b, the splice variant of human MNK1a, is constitutively active and independent of upstream MAP kinases. In this study, we have analyzed the expression of both MNK1 isoforms in 69 breast tumor samples and its association with clinicopathologic/prognostic characteristics of breast cancer. MNK1a and MNK1b expression was significantly increased in tumors relative to the corresponding adjacent normal tissue (p < 0.001). In addition, MNK1b overexpression was found in most of the triple-negative tumors and was associated with a shorter overall and disease-free survival time. Overexpression of MNK1b in MDA-MB-231 cells induced an increase in the expression of the MCL1 antiapoptotic protein and promoted proliferation, invasion and colony formation. In conclusion, a high expression level of MNK1b protein could be used as a marker of poor prognosis in breast cancer patients and it could be a therapeutic target in triple-negative tumors.
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A comparison between the free-energy surfaces of the all- trans-retinal protonated Schiff base (RPSB) and its 10-methylated derivative in gas phase and methanol solution is performed at CASSCF//CASSCF and CASPT2//CASSCF levels. Solvent effects were included using the average solvent electrostatic potential from molecular dynamics method. This is a QM/MM (quantum mechanics/molecular mechanics) method that makes use of the mean field approximation. It is found that the methyl group bonded to C10 produces noticeable changes in the solution free-energy profile of the S1 excited state, mainly in the relative stability of the minimum energy conical intersections (MECIs) with respect to the Franck-Condon (FC) point. The conical intersections yielding the 9- cis and 11- cis isomers are stabilized while that yielding the 13- cis isomer is destabilized; in fact, it becomes inaccessible by excitation to S1. Furthermore, the planar S1 minimum is not present in the methylated compound. The solvent notably stabilizes the S2 excited state at the FC geometry. Therefore, if the S2 state has an effect on the photoisomerization dynamics, it must be because it permits the RPSB population to branch around the FC point. All these changes combine to speed up the photoisomerization in the 10-methylated compound with respect to the native compound.
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Substituent and solvent effects on the excited state dynamics of the Photoactive Yellow Protein chromophore are studied using the average solvent electrostatic potential from molecular dynamics (ASEP/MD) method. Four molecular models were considered: the ester and thioester derivatives of the p-coumaric acid anion and their methylated derivatives. We found that the solvent produces dramatic modifications on the free energy profile of the S1 state: 1) Two twisted structures that are minima in the gas phase could not be located in aqueous solution. 2) Conical intersections (CIs) associated with the rotation of the single bond adjacent to the phenyl group are found for the four derivatives in water solution but only for thio derivatives in the gas phase. 3) The relative stability of minima and CIs is reverted with respect to the gas phase values, affecting the prevalent de-excitation paths. As a consequence of these changes, three competitive de-excitation channels are open in aqueous solution: the fluorescence emission from a planar minimum on S1, the trans-cis photoisomerization through a CI that involves the rotation of the vinyl double bond, and the nonradiative, nonreactive, de-excitation through the CI associated with the rotation of the single bond adjacent to the phenyl group. In the gas phase, the minima are the structures with the lower energy, while in solution these are the conical intersections. In solution, the de-excitation prevalent path seems to be the photoisomerization for oxo compounds, while thio compounds return to the initial trans ground state without emission.