RESUMEN
Acid mine drainage (AMD) is the major effluent generated from metal and coal mines, causing serious ecological risks and degradation of aquatic habitats and surrounding soil quality. Biochemical passive reactors (BPRs) are an option for improving AMD affected water. This study investigates the effect of the size and concentration of zerovalent iron nanoparticles (nZVI) on the efficiency of batch BPRs during AMD remediation. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) were also used as complementary techniques for the investigation of the changes in microbial cells and nZVI properties after the AMD remediation. The results from the batch experiment showed that the concentration of nZVI increases the pH and decreases ORP during AMD treatment, thus favouring the removal of metals. The results also suggest that metal sulfide precipitation occurred in all the batch with reactive mixture but was greater in reactors amended with nZVI of larger size. This study revealed that the presence of nZVI in the BPR leads to metal removal as well as the inhibition of sulfate-reducing bacteria (SRB) activity. Microscopy study indicated that the addition of nZVI creates a morphological change on certain microorganisms in which the cellular membrane was fully covered with nZVI, inducing cell lysis process. These results show that nZVI is a promising reactive material for the treatment of AMD in BPR systems.
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Nanopartículas , Contaminantes Químicos del Agua , Ácidos/química , Hierro/química , Metales , Minería , Contaminantes Químicos del Agua/químicaRESUMEN
Plants of the Calea genus have been reported to contain lipophilic compounds, such as sesquiterpene lactones, with cytotoxic effect against different cancer cell lines. The aim of this manuscript was to investigate the chemical profile and cytotoxic activity of different fractions from Calea phylolepis leaves on different human cancer cell lines. The fractions were prepared using solvent extraction of increasing polarity, yielding hexane, ethyl acetate and methanolic fractions. All fractions were chemically analysed by thin layer chromatography (TLC), and their cytotoxic activity against HT-29 (colon adenocarcinoma), MCF-7 (breast cancer), U-251MG (malignant glioblastoma) and L929 (mouse fibroblast) cell lines was investigated. Among these, the hexane and ethyl acetate fractions showed higher cytotoxic effects, while the methanolic fraction did not show any cytotoxic effects. The major bioactive compound from the hexane fraction (12.15%) was isolated using chromatographic methods and was identified by nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS) analysis as 6-epi-ß-verbesinol coumarate. This compound showed activity against breast cancer cells (IC50 = 5.8 ± 1.0 µg/ml), similar to etoposide. Furthermore, 6-epi-ß-verbesinol coumarate showed low cytotoxicity to normal fibroblast cells, suggesting a high selectivity index (SI = 7.39) against breast cancer cells.
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Antineoplásicos Fitogénicos/farmacología , Asteraceae/química , Neoplasias de la Mama/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/toxicidad , Línea Celular , Línea Celular Tumoral , Femenino , Fibroblastos/efectos de los fármacos , Cromatografía de Gases y Espectrometría de Masas , Células HT29 , Humanos , Concentración 50 Inhibidora , Células MCF-7 , Espectroscopía de Resonancia Magnética , Ratones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/toxicidad , Hojas de la PlantaRESUMEN
Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 µg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantiï¬ed. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds
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Turquía/etnología , Células/metabolismo , Eryngium/anatomía & histología , Fitoquímicos/efectos adversos , Preparaciones Farmacéuticas/administración & dosificación , Línea Celular/clasificación , Células A549/metabolismo , Acetatos/administración & dosificaciónRESUMEN
In this work, the synthesis of SrB4O7 through solid state reaction and its beta particle excited thermoluminescence (TL) are reported. The glow curves show maxima around 200 and 300 -considered suitable for TL dosimetry-, and a remarkable reproducibility in successive irradiation - TL readout cycles. The integrated TL exhibits a linear dependence upon the irradiation dose in the tested dose range (from 1.0 up to 8.0 Gy). The lower detection limit and the sensitivity relative to the TLD-100 dosimeter are 88 mGy and 0.49, respectively. From the results here presented, we conclude that SrB4O7 synthesized through solid state reaction can be considered a phosphor material interesting to develop TL dosimeters.
RESUMEN
Sulfate and chemical oxygen demand removal by an anaerobic batch reactor treating of acid mine drainage is modelled. Available models are abundant but excessively complex, with large numbers of free parameters. Here, maximum likelihood and chi-squared hypothesis tests are applied to three simple models, with Malthus-Monod and Fick description, in increasing order of complexity: (i) planktonic single population (of sulfate-reducing bacteria); (ii) planktonic double-competing populations (adding fermentative bacteria); (iii) granule bound double-competing populations. The data set consists of 6 time profiles, sampled from 120 days of operation after stabilization of the reactor in pH 4. Single population is refuted by all profiles, in which the sulfate reduction is 72% larger than fermentatives. The planktonic double-competing population description is refuted at 119 days, with inner granule diffusion rate as low as 10% of the previous period. The results showed that, after an operation time, the influence of mass transfer became more evident and the incorporation of Fick's law in the model was fundamental to the description of this trend. All tests and inferences are performed at the 90% confidence interval due to large systematic uncertainties in the data.
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Reactores Biológicos , Sulfatos , Ácidos , Análisis de la Demanda Biológica de Oxígeno , MineríaRESUMEN
Abstract Curcumin (CUR) shows potential use for treating cancer. However, CUR has low solubility and reduced bioavailability, which limit its clinical effect. Therefore, the development of nanocarriers can overcome these problems and can ensure the desired pharmacological effect. In addition, it is mandatory to prove the quality, the efficacy, and the safety for a novel nanomedicine to be approved. In that sense, this paper aimed (a) to prepare CUR-loaded polyethylene glycol-poly(ε-caprolactone) nanocapsules; (b) to validate an analytical method by high performance liquid chromatography (HPLC) for quantifying CUR in these nanoformulations; (c) to evaluate the physicochemical stability of these formulations; and to investigate their cytotoxicity on NIH-3T3 mouse fibroblast cells. The HPLC method was specific to CUR in the loaded nanocapsules, linear (r = 0.9994) in a range of 10.0 to 90.0 µg.mL-1 with limits of detection and quantification of 0.160 and 0.480 µg.mL-1, respectively. Precision was demonstrated by a relative standard deviation lower than 5%. Suitable accuracy (102.37 ± 0.92%) was obtained. Values of pH, particle size, polydispersity index, and zeta potential presented no statistical difference (p > 0.05) for CUR-loaded nanoparticles. No cytotoxicity was observed against NIH-3T3 mouse embryo fibroblast cell line using both the tetrazolium salt and sulforhodamine B assays. In conclusion, a simple and inexpensive HPLC method was validated for the CUR quantification in the suspensions of nanocapsules. The obtained polymeric nanocapsules containing CUR showed suitable results for all the performed assays and can be further investigated as a feasible novel approach for cancer treatment.
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Animales , Ratones , Curcumina/farmacología , Células Madre Embrionarias/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Pruebas de Toxicidad , Nanotecnología , Células 3T3 NIH , Embrión de Mamíferos/citología , NanocápsulasRESUMEN
The geothermal Copahue-Caviahue (GCC) system (Argentina) is an extreme acidic environment, dominated by the activity of Copahue volcano. Environments characterised by low pH values, such as volcanic areas, are of particular interest for the search of acidophilic microorganisms with application in biotechnological processes. In this work, sulfate-reducing microorganisms were investigated in geothermal acidic, anaerobic zones from GCC system. Sediment samples from Agua del Limón (AL1), Las Máquinas (LMa2), Las Maquinitas (LMi) and Baño 9 (B9-2, B9-3) were found to be acidic (pH values 2.1-3.0) to moderate acidic (5.1-5.2), containing small total organic carbon values, and ferric iron precipitates. The organic electron donor added to the enrichment was completely oxidised to CO2. Bacteria related to 'Desulfobacillus acidavidus' strain CL4 were found to be dominant (67-83% of the total number of clones) in the enrichment cultures, and their presence was confirmed by their isolation on overlay plates. Other bacteria were also detected with lower abundance (6-20% of the total number of clones), with representatives of the genera Acidithiobacillus, Sulfobacillus, Alicyclobacillus and Athalassotoga/Mesoaciditoga. These enrichment and isolates found at low pH confirm the presence of anaerobic activities in the acidic sediments from the geothermal Copahue-Caviahue system.
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Bacterias/clasificación , Bacterias/aislamiento & purificación , Sedimentos Geológicos/microbiología , Manantiales de Aguas Termales/microbiología , Ácidos , Argentina , Bacterias/genética , Ambiente , Concentración de Iones de Hidrógeno , Hierro/metabolismo , Oxidación-Reducción , Filogenia , ARN Ribosómico 16S/genética , Sulfatos/metabolismoRESUMEN
In this study, a series of C-28 amides derivatives of hederagenin with or without the presence of an acetyl group at positions 3 and 23 in ring A, were synthetized aiming to develop potent cytotoxic agents. Their structures were confirmed by MS, IR, 1H NMR and 13C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. The majority of the amide derivatives were cytotoxic for a variety of human tumor cell lines. In general, the hydroxylated derivatives (1a-1d; EC50 in the range 1.2-22.5⯵M) were less active than the acetylated derivatives (2a-2n; EC50 in the range 0.4-9.0⯵M). Hydroxylated derivative bearing pyrrolidinyl substituent 1c, was the most active for HT29 human line cells (EC50â¯=â¯1.2⯵M), however their acetylated derivative 2c was the most potent and selective against A2780, FaDu, SW1736â¯cells, showing EC50 values between 0.4 and 1.7⯵M and SI between 5.6 and 24. Staining experiments combined with fluorescence microscopy indicate that the cell membrane became permeable, and finally a process of secondary necrosis was observed. In addition, the docking results showed that acetylated compounds display more affinity to HER2 than to USP7, indicating that HER2 is a most probable receptor, both proteins found in tumor cell line A2780.
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Amidas/farmacología , Antineoplásicos/farmacología , Ácido Oleanólico/análogos & derivados , Amidas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Microscopía Fluorescente , Simulación del Acoplamiento Molecular , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Relación Estructura-ActividadRESUMEN
Surfactants and co-surfactants play an important role in enhanced oil recovery for they improve petroleum solubility and reduce interfacial tensions between oil, water and the rock formation. Ethanol is receiving renewed attention as potential co-surfactant because of the negative results obtained with the use of salts and alkaline substances. Sulphate-reducing bacteria (SRB) can use surfactants and co-surfactants as carbon sources and, consequently, this can increase the biological accumulation of sulphide (souring). The aim of this research is to correlate SRB activity with different concentrations of co-surfactant (ethanol) as an attempt to quantifying in which concentration such compound can potentially increase or inhibit souring. The results show that the combination of surfactant (lauryl glucoside) and co-surfactant (ethanol) can increase SRB activity to about 2.3-fold. The highest sulphate consumption rate of 591â µgâ l-1â h-1 was observed in experiments with 0.03% and 1.5% (v/v) of surfactant and ethanol, respectively. The experiments indicated that SRB activity is only controlled by ethanol concentrations above 6.5% (v/v). Ethanol can potentially decrease costs with the use of biocides and significantly increase oil recovery ratios. Tests with the model Desulfovibrio vulgaris were not comparable with the results obtained with the SRB consortium.
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Desulfovibrio , Petróleo , Sulfatos , Sulfuros , TensoactivosRESUMEN
Scavenger receptor class B type 1 (SR-B1) plays an essential role in high density lipoprotein (HDL) metabolism. SR-B1 deficient (SR-B1 KO) mice are prone to atherosclerosis and exhibit abnormally large, cholesterol-rich, dysfunctional HDL. In a recent issue of J Transl Med, Cao et al. described results of proteomics analyses of HDL isolated from wild-type (WT) and SR-B1 KO mice using precipitation of large lipoproteins with polyethylene glycol (PEG). They report abnormalities in SR-B1 KO HDL protein components that correlate with HDL function. In this commentary, we describe and discuss the differences in the results published by Cao et al. and those obtained in a recent study from our laboratory using shotgun proteomics of HDL of SR-B1 KO mice isolated by ultracentrifugation. We propose that different HDL purification procedures used may account for the discrepancies observed. We show that SR-B1 KO HDL purification using either PEG or dextran sulfate precipitation results in enrichment of small HDL subclasses, and may therefore underestimate alterations in lipoprotein composition or function. Compared to HDL obtained by ultracentrifugation, HDL isolated by PEG precipitation show a lower ApoE/ApoA-I proportion and reduced cholesterol content. HDL protein components described by Cao et al. or our laboratory are mostly inconsistent: only 33 HDL proteins were detected in both datasets, whereas a significant number of proteins were only identified by Cao et al. (n = 43) or Contreras-Duarte et al. (n = 26) datasets. The relative abundance of HDL-associated peptide and protein levels in WT vs SR-B1 HDL were also highly different in both datasets. This study indicates that caution must be taken when interpreting results from HDL isolated by chemical precipitation.
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HDL-Colesterol/metabolismo , Proteoma/metabolismo , Receptores Depuradores de Clase B/deficiencia , Animales , Precipitación Química , HDL-Colesterol/sangre , Ratones Noqueados , Proteómica , Receptores Depuradores de Clase B/metabolismoRESUMEN
Alzheimer's disease (AD) is associated with a progressive dementia, and there is good evidence that it is more pronounced in individuals that have fewer stimuli during their lives. Environmental stimulation promotes morphological and functional changes in the brain, leading to amplification of cognitive functions, and has been described in humans and animals. In this study, we evaluated the effects of enriched environment (EE) stimulation on spatial memory and senile plaque formation in transgenic mice PDGFB-APPSwInd (TG) that overexpress the human amyloid precursor protein, normally resulting in an increased density of senile plaques. We compared this group of EE stimulated transgenic mice (TG-EE) with an EE stimulated control group of age-matched C57Bl/6 wild type animals (WT-EE). Both groups were exposed to EE stimulation between the ages of 8 and 12 months. As controls of the experiment, there were a group of TG mice not exposed to EE (TG-Ctrl) and a group of WT mice not exposed to EE (WT-Ctrl). The TG-EE group presented improved spatial memory when compared to the TG-Ctrl animals. In addition, the TG-EE group showed a 69.2% reduction in the total density of senile plaques in the hippocampus when compared to the TG-Ctrl group. In this group, the concentration of senile plaques was greater in the dorsal part of the hippocampus, which is linked to spatial localization, and the reduction of this density after the submission to EE was as high as 85.1%. EE stimulation had no effect on the density of amyloid-ß (Aß) oligomers. However, amyloid scavenger receptor class B member 1 (SR-B1) density was significantly decreased in the TG-Ctrl mice, but not in the TG-EE mice, suggesting that cognitive stimulation had an effect on the formation of a cognitive reserve that could prevent the accumulation of senile plaques. It is suggested that the stimulation of old mice by EE for 4 months led to the formation of brain resilience that protected the brain from the deposition of senile plaques, one of the hallmarks of AD, leading to improvement in spatial memory.
RESUMEN
BACKGROUND: The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD. RESULTS: We used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryos were enriched for functions associated to neural development, while up-regulated genes in KO-NTD embryos were enriched for functions related to lipid metabolism. Feeding pregnant dams a vitamin E-enriched diet, which prevents NTD in SR-B1 KO embryos, resulted in mRNA levels for those differentially expressed genes that were more similar to KO-N than to KO-NTD embryos. We used gene regulatory network analysis to identify putative transcriptional regulators driving the different embryonic expression profiles, and identified a regulatory circuit controlled by the androgen receptor that may contribute to this dichotomous expression profile in SR-B1 embryos. Supporting this possibility, the expression level of the androgen receptor correlated strongly with the expression of several genes involved in neural development and lipid metabolism. CONCLUSIONS: Our analysis shows that normal and defective embryos lacking SR-B1 have divergent expression profiles, explained by a defined set of transcription factors that may explain their divergent phenotype. We propose that distinct expression profiles may be relevant during early development to support embryonic nutrition and neural tube closure.
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Antígenos CD36/deficiencia , Antígenos CD36/genética , Perfilación de la Expresión Génica , Técnicas de Inactivación de Genes , Redes Reguladoras de Genes , Tubo Neural/embriología , Transcripción Genética , Animales , Humanos , Ratones , Tubo Neural/metabolismo , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/metabolismo , Fenotipo , DesteteRESUMEN
Strategies for the control of sulfate-reducing bacteria (SRB) in the oil industry involve the use of high concentrations of biocides, but these may induce bacterial resistance and/or be harmful to public health and the environment. Essential oils (EO) produced by plants inhibit the growth of different microorganisms and are a possible alternative for controlling SRB. We aimed to characterize the bacterial community of produced water obtained from a Brazilian petroleum facility using molecular methods, as well as to evaluate the antimicrobial activity of EO from different plants and their major components against Desulfovibrio alaskensis NCIMB 13491 and against SRB growth directly in the produced water. Denaturing gradient gel electrophoresis revealed the presence of the genera Pelobacter and Marinobacterium, Geotoga petraea, and the SRB Desulfoplanes formicivorans in our produced water samples. Sequencing of dsrA insert-containing clones confirmed the presence of sequences related to D. formicivorans. EO obtained from Citrus aurantifolia, Lippia alba LA44 and Cymbopogon citratus, as well as citral, linalool, eugenol and geraniol, greatly inhibited (minimum inhibitory concentration (MIC) = 78 µg/mL) the growth of D. alaskensis in a liquid medium. The same MIC was obtained directly in the produced water with EO from L. alba LA44 (containing 82% citral) and with pure citral. These findings may help to control detrimental bacteria in the oil industry.
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Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Industria del Petróleo y Gas , Aceites Volátiles/farmacología , Sulfatos/metabolismo , Agua , Bacterias/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
In this study, we explore the cytotoxic activity of four natural abenquines (2a-d) and fourteen synthetic analogues (2e-j and 3a-h) against a panel of six human cancer cell lines using a SRB assay. It was found that most of the compounds revealed higher levels of cytotoxic activities than naturally occurring abenquines. The analogues carrying ethylpyrrolidinyl and ethylpyrimidinyl with either an acetyl group (2h-i) or a benzoyl group (3f-g), were the most potent against all human cancer cell lines and displayed EC50 between a range of 0.6-3.4µM. Notably, of the compounds tested, compound 2i proved the most cytotoxic against both ovarian (A2780) and breast (MCF7) cells, showing EC50=0.6 and 0.8µM respectively. Likewise, the analogues 2i, 3f and 3g showed strong activity against cell HT29 with EC50=0.9µM for these compounds.
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Antineoplásicos/farmacología , Quinonas/farmacología , Células 3T3 , Animales , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Quinonas/químicaRESUMEN
Biochemical passive treatment represents a promising option for the remediation of acid mine drainage. This study determined the effect of three hydraulic retention times (1, 2, and 4 days) on changes in system efficiency, reactive mixture, and microbial activity in bioreactors under upward flow conditions. Bioreactors were sacrificed in the weeks 8, 17 and 36, and the reactive mixture was sampled at the bottom, middle, and top layers. Physicochemical analyses were performed on reactive mixture post-treatment and correlated with sulfate-reducing bacteria and cellulolytic and dehydrogenase activity. All hydraulic retention times were efficient at increasing pH and alkalinity and removing sulfate (>60%) and metals (85-99% for Fe(2+) and 70-100% for Zn(2+)), except for Mn(2+). The longest hydraulic retention time (4 days) increased residual sulfides, deteriorated the quality of treated effluent and negatively impacted sulfate-reducing bacteria. Shortest hydraulic retention time (1 day) washed out biomass and increased input of dissolved oxygen in the reactors, leading to higher redox potential and decreasing metal removal efficiency. Concentrations of iron, zinc and metal sulfides were high in the bottom layer, especially with 2 day of hydraulic retention time. Sulfate-reducing bacteria, cellulolytic and dehydrogenase activity were higher in the middle layer at 4 days of hydraulic retention time. Hydraulic retention time had a strong influence on overall performance of passive reactors.
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Bacterias/metabolismo , Reactores Biológicos/microbiología , Drenaje de Agua/métodos , Minería/métodos , Administración de Residuos/métodos , Ácidos/química , Biomasa , Concentración de Iones de Hidrógeno , Metales/química , Oxidación-Reducción , Oxígeno/química , Sulfatos/química , Sulfuros/químicaRESUMEN
A series of novel aryl-1H-1,2,3-triazol-4-yl methylester and amide derivatives of the natural product hederagenin was synthesized aiming to develop new antitumor agents, using Huisgen 1,3-dipolar cycloaddition reactions, with yields between 35% and 95%. The structures of all derivatives (2-31) were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic data. The cytotoxic activities of all compounds were screened against a panel of six human cancer cell lines using SRB assay. It was found that most of the compounds displayed higher levels of antitumor activities as compared to parent hederagenin. Compounds 4, 8 and 15 were the most potent against all human cancer cell lines. Furthermore, compound 11 was the most cytotoxic against cell HT29 showing EC50 = 1.6 µM and a selectivity index of 5.4.
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Antineoplásicos/farmacología , Ácido Oleanólico/análogos & derivados , Triazoles/química , Antineoplásicos/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ácido Oleanólico/químicaRESUMEN
In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, (1)H NMR and (13)C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. Although most of the compounds displayed moderate to high levels of cytotoxic activity they were all more potent than the natural product He. The most active compounds had either an ethylpyrimidinyl (27) or an ethylpyrrolidinyl (28) substituent, with EC50 in the range of 1.1-6.5 µM for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He.
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Antineoplásicos/química , Antineoplásicos/farmacología , Ácido Oleanólico/análogos & derivados , Antineoplásicos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Relación Estructura-ActividadRESUMEN
We have used docking techniques in order to propose potential inhibitors to the enzymes adenosine phosphosulfate reductase and adenosine triphosphate sulfurylase that are responsible, among other deleterious effects, for causing souring of oil and gas reservoirs. Three candidates selected through molecular docking revealed new and improved polar and hydrophobic interactions with the above-mentioned enzymes. Microbiological laboratory assays performed subsequently corroborated the results of computer modelling that the three compounds can efficiently control the biogenic sulfide production.
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Ligandos , Simulación del Acoplamiento Molecular , Sitios de Unión , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Modelos Moleculares , Conformación Molecular , Simulación de Dinámica Molecular , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/antagonistas & inhibidores , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/química , Unión Proteica , Sulfato Adenililtransferasa/antagonistas & inhibidores , Sulfato Adenililtransferasa/químicaRESUMEN
The biogenic production of hydrogen sulfide gas by sulfate-reducing bacteria (SRB) causes serious economic problems for natural gas and oil industry. One of the key enzymes important in this biologic process is adenosine phosphosulfate reductase (APSr). Using virtual screening technique we have discovered 15 compounds that are novel potential APSr inhibitors. Three of them have been selected for molecular docking and microbiological studies which have shown good inhibition of SRB in the produced water from the oil industry.
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Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/antagonistas & inhibidores , Contaminantes Químicos del Agua/química , Bacterias/metabolismo , Proteínas Bacterianas/química , Industria Procesadora y de Extracción , Aceites Combustibles , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/metabolismo , Microbiología Industrial , Simulación de Dinámica Molecular , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/química , Aguas Residuales/química , Purificación del AguaRESUMEN
Several novel 2,4-dinitrophenylhydrazone betulinic acid derivatives have been prepared by chemical and biotransformation methods using fungi and carrot cells. Some compounds showed significant cytotoxicity and selectivity against some tumor cell lines. The most active, 3-[(2,4-dinitrophenyl)hydrazono]lup-(20R)-29-oxolupan-28-oic acid, showed IC50 values between 1.76 and 2.51 µM against five human cancer cell lines. The most selective, 3-hydroxy-20-[(2,4-dinitrophenyl)hydrazono]-29-norlupan-28-oic acid, was five to seven times more selective for cancer cells when compared to fibroblasts. Cell cycle analysis and apoptosis induction were studied for the most active derivatives.