RESUMO
The most crucial role played by minerals was in the preconcentration of biomolecules or precursors of biomolecules in prebiotic seas. If this step had not occurred, molecular evolution would not have occurred. Thiocyanate is an important molecule in the formation of biomolecules as well as a catalyst for prebiotic reactions. The adsorption of thiocyanate onto ferrihydrite was carried out under pH and ion composition conditions in seawater that resembled those of prebiotic Earth. The seawater used in this work had high Mg2+, Ca2+ and SO42- concentrations. The most important result of this work was that ferrihydrite adsorbed thiocyanateata pH value (7.2 ± 0.2) that usually does not adsorb thiocyanate. The high adsorptivity of Mg2+, Ca2+ and SO42-onto ferrihydrite showed that seawater ions can act as carriers of thiocyanate to the ferrihydrite surface, creating a huge outer-sphere complex. Kinetic adsorption and isotherm experiments showed the best fit for the pseudo-second-order model and an activation energy of 23.8 kJ mol-1forthe Langmuir-Freundlich model, respectively. Thermodynamic data showed positive ΔG values, which apparently contradict the adsorption isotherm data and kinetic data that was obtained. The adsorption of thiocyanate onto ferrihydrite could be explained by coupling with the exergonic SO42- adsorption onto ferrihydrite. The FTIR spectra showed no difference between the C≡N stretching peaks of adsorbed thiocyanate and free thiocyanate, corroborating the formation of an outer-sphere complex. All the results demonstrated the importance of the artificial seawater composition for the adsorption of thiocyanate and for understanding prebiotic chemistry.
Assuntos
Compostos Férricos/química , Origem da Vida , Tiocianatos/química , Adsorção , Evolução PlanetáriaRESUMO
As a continuation of our project aimed at searching for new chemotherapeutic agents against American trypanosomiasis (Chagas disease), new selenocyanate derivatives were designed, synthesized and biologically evaluated against the clinically more relevant dividing form of Trypanosoma cruzi, the etiologic agent of this illness. In addition, in order to establish the role of each part of the selenocyanate moiety, different derivatives, in which the selenium atom or the cyano group were absent, were conceived, synthesized and biologically evaluated. In addition, in order to study the optimal position of the terminal phenoxy group, new regioisomers of WC-9 were synthesized and evaluated against T. cruzi. Finally, the resolution of a racemic mixture of a very potent conformationally rigid analogue of WC-9 was accomplished and further tested as growth inhibitors of T. cruzi proliferation. The results provide further insight into the role of the selenocyanate group in its antiparasitic activity.
Assuntos
Antiparasitários/farmacologia , Compostos Organosselênicos/farmacologia , Éteres Fenílicos/farmacologia , Tiocianatos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiparasitários/síntese química , Antiparasitários/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Testes de Sensibilidade Parasitária , Éteres Fenílicos/química , Relação Estrutura-Atividade , Tiocianatos/química , Células VeroRESUMO
We report on the low energy anion spectra of 5-cyanateuracil (5-OCNU) and 5-thiocyanateouracil (5-SCNU), which have been the suggested potential radiosensitizers for use in cancer therapy [L. Chomicz et al., J. Phys. Chem. Lett. 4, 2853-2857 (2013)]. Employing bound state and scattering calculations, we obtained, for both molecules, a dipole bound state, a π* valence bound state, and four π* resonances, besides a σSCN* resonance for 5-SCNU. The cyanate and thiocyanate substituents give rise to additional long-lived π* resonances, compared to 5-halouracil radiosensitizers. From the reaction thresholds and the expected vibronic couplings among the anion states, efficient production of SCN and CN anions and radical fragments should be observed in dissociative electron attachment measurements for 5-SCNU. The corresponding dissociation processes in 5-OCNU are expected to be less effective in view of the lack of a long-lived σOCN* shape resonance and the little σ* admixture into the π* resonances located on the cyanate group. The present results thus indicate 5-SCNU as a more promising radiosensitizer at sub-excitation energies.
Assuntos
Cianatos/química , Radiossensibilizantes/química , Tiocianatos/química , Uracila/análogos & derivados , Ânions/química , Modelos MolecularesRESUMO
The obligate intracellular parasite, Trypanosoma cruzi is the etiologic agent of Chagas disease or American trypanosomiasis, which is the most prevalent parasitic disease in the Americas. The present chemotherapy to control this illness is still deficient particularly in the chronic stage of the disease. The ergosterol biosynthesis pathway has received much attention as a molecular target for the development of new drugs for Chagas disease. Especially, inhibitors of the enzymatic activity of squalene synthase were shown to be effective compounds on T. cruzi proliferation in in vitro assays. In the present study we designed, synthesized and evaluated the effect of a number of isosteric analogues of WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, on T. cruzi growth in tissue culture cells. The selenium-containing derivatives turned out to be extremely potent inhibitors of T. cruzi growth. Certainly, 3-phenoxyphenoxyethyl, 4-phenoxyphenoxyethyl, 4-(3-fluorophenoxy)phenoxyethyl, 3-(3-fluorophenoxy)phenoxyethyl selenocyanates and (±)-5-phenoxy-2-(selenocyanatomethyl)-2,3-dihydrobenzofuran arose as relevant members of this family of compounds, which exhibited effective ED50 values of 0.084⯵M, 0.11⯵M, 0.083,⯵M, 0.085, and 0.075⯵M, respectively. The results indicate that compounds bearing the selenocyanate moiety are at least two orders of magnitude more potent than the corresponding skeleton counterpart bearing the thiocyanate group. Surprisingly, these compounds exhibited excellent selectively index values ranging from 900 to 1800 making these molecules promising candidates as antiparasitic agents.
Assuntos
Éteres Fenílicos/farmacologia , Selênio/farmacologia , Tiocianatos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Estrutura Molecular , Testes de Sensibilidade Parasitária , Éteres Fenílicos/síntese química , Éteres Fenílicos/química , Selênio/química , Relação Estrutura-Atividade , Tiocianatos/síntese química , Tiocianatos/química , Tripanossomicidas/síntese química , Tripanossomicidas/química , Trypanosoma cruzi/citologia , Trypanosoma cruzi/crescimento & desenvolvimento , Células VeroRESUMO
Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T.â cruzi and T.â gondii growth in tissue culture cells. Two fluorine-containing derivatives, the 3-(3-fluorophenoxy)- and 3-(4-fluorophenoxy)phenoxyethyl thiocyanates, exhibited half-maximal effective concentration (EC50 ) values of 1.6 and 4.9â µm, respectively, against tachyzoites of T.â gondii, whereas they showed similar potency to WC-9 against intracellular T.â cruzi (EC50 values of 5.4 and 5.7â µm, respectively). In addition, 2-[3- (phenoxy)phenoxyethylthio]ethyl-1,1-bisphosphonate, which is a hybrid inhibitor containing 3-phenoxyphenoxy and bisphosphonate groups, has activity against T.â gondii proliferation at sub-micromolar levels (EC50 =0.7â µm), which suggests a combined inhibitory effect of the two functional groups.
Assuntos
Flúor/química , Modelos Moleculares , Éteres Fenílicos/farmacologia , Tiocianatos/farmacologia , Toxoplasma/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiparasitários/química , Antiparasitários/farmacologia , Chlorocebus aethiops , Simulação por Computador , Cristalografia por Raios X , Humanos , Éteres Fenílicos/química , Homologia de Sequência do Ácido Nucleico , Tiocianatos/química , Células VeroRESUMO
Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3ß-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED50values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level.
Assuntos
Antiparasitários/farmacologia , Doença de Chagas/tratamento farmacológico , Desenho de Fármacos , Éteres Fenílicos/farmacologia , Tiocianatos/farmacologia , Toxoplasmose/tratamento farmacológico , Animais , Antiparasitários/química , Antiparasitários/uso terapêutico , Humanos , Éteres Fenílicos/química , Éteres Fenílicos/uso terapêutico , Tiocianatos/química , Tiocianatos/uso terapêutico , Toxoplasma/efeitos dos fármacos , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
A high-yielding method for the direct thiocyanation of BODIPY dyes is described. In 1,3-dimethyl BODIPYs, the thiocyanato group adds at position 2, whereas the insertion occurs at position 5 in 3-amino BODIPYs. The transformation of the thiocyanato group enables the synthesis of thioalkylated BODIPYs. 2-Thioalkylated BODIPYs and 3-thiocyanato-5-piperidino BODIPYs exhibit interesting spectroscopical features. Hence, the described synthetic methodology can be used for the photophysical tuning of BODIPY dyes.
Assuntos
Compostos de Boro/química , Corantes Fluorescentes/síntese química , Tiocianatos/química , Alquilação , Compostos de Boro/síntese química , Cristalografia por Raios X , Corantes Fluorescentes/química , Tiocianatos/síntese químicaRESUMO
A flow-based system with solenoid micro-pumps and long path-length spectrophotometry for bromate and bromide determination in drinking water is proposed. The method is based on the formation of an unstable dye from the reaction between bromate, 2-(5-dibromo-2-pyridylazo)-5-(diethylamino)phenol (5-Br-PADAP) and thiocyanate ions. A multivariate optimization was carried out. A linear response was observed between 5.0 and 100 µg L(-1) BrO3(-) and the detection limit was estimated as 2.0 µg L(-1) (99.7% confidence level). The coefficient of variation (n=20) and sampling rate were estimated as 1.0% and 40 determinations per hour, respectively. Reagent consumption was estimated as 0.17 µg of 5-Br-PADAP and 230 µg of NaSCN per measurement, generating 6.0 mL of waste. Bromide determination was carried out after UV-assisted conversion with K2S2O8 using 300 µL of sample within the range 20-400 µg L(-1) Br(-). The generated bromate was then determined by the proposed flow system. The results for tap and commercial mineral water samples agreed with those obtained with the reference procedure at the 95% confidence level. The proposed procedure is therefore a sensitive, environmentally friendly and reliable alternative for inorganic bromine speciation.
Assuntos
Bromo/análise , Espectrofotometria Ultravioleta/métodos , Poluentes Químicos da Água/análise , Compostos Azo/química , Brometos/química , Cloretos/química , Modelos Lineares , Oxigênio/química , Fotoquímica/métodos , Reprodutibilidade dos Testes , Sulfatos/química , Tiocianatos/química , Raios Ultravioleta , Água/análise , Água/química , Abastecimento de ÁguaRESUMO
Background Rhizoctonia solani (teleomorph: Thanatephorus cucumeris) is one of the most important pathogens of rice (Oryza sativa L.) that causes severe yield losses in all rice-growing regions. Sclerotia, formed from the aggregation of hyphae, are important structures in the life cycles of R. solani and contain a large quantity of polysaccharides, lipids, proteins and pigments. In order to extract high-quality total RNA from the sclerotia of R. solani, five methods, including E.Z.N.A.™ Fungal RNA Kit, sodium dodecyl sulfate (SDS)-sodium borate, SDS-polyvinylpyrrolidone (PVP), guanidinium thiocyanate (GTC) and modified Trizol, were compared in this study. Results The electrophoresis results showed that it failed to extract total RNA from the sclerotia using modified Trizol method, whereas it could extract total RNA from the sclerotia using other four methods. Further experiments confirmed that the total RNA extracted using SDS-sodium borate, SDS-PVP and E.Z.N.A.™ Fungal RNA Kit methods could be used for RT-PCR of the specific amplification of GAPDH gene fragments, and that extracted using GTC method did not fulfill the requirement for above-mentioned RT-PCR experiment. Conclusion It is concluded that SDS-sodium borate and SDS-PVP methods were the better ones for the extraction of high-quality total RNA that could be used for future gene cloning and expression studies, whereas E.Z.N.A.™ Fungal RNA Kit was not taken into consideration when deal with a large quantity of samples because it is expensive and relatively low yield.
Assuntos
Rhizoctonia/genética , RNA/isolamento & purificação , Fenóis/química , Dodecilsulfato de Sódio/química , Tiocianatos/química , Boratos/química , RNA Fúngico/genética , Povidona/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Eletroforese , Guanidinas/químicaRESUMO
As a part of our project pointed at the search of new safe chemotherapeutic and chemoprophylactic agents against parasitic diseases, several compounds structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were modified at the terminal aromatic ring, were designed, synthesized and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible of American trypanosomiasis (Chagas disease) and Toxoplasma gondii, the etiological agent of toxoplasmosis. Most of the synthetic analogs exhibited similar antiparasitic activity being slightly more potent than the reference compound WC-9. For example, the nitro derivative 13 showed an ED50 value of 5.2 µM. Interestingly, the regioisomer of WC-9, compound 36 showed similar inhibitory action than WC-9 indicating that para-phenyl substitution pattern is not necessarily required for biological activity. The biological evaluation against T. gondii was also very promising. The ED50 values corresponding for 13, 36 and 37 were at the very low micromolar level against tachyzoites of T. gondii.