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1.
ACS Sens ; 6(3): 1295-1304, 2021 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-33544583

RESUMEN

Humidity- and temperature-dependent errors in concentrations reported by electrochemical sensors for atmospheric nitrogen dioxide significantly limit the reliability of the data. A basic understanding of the source of these errors has been missing. Empirical, software-based corrections are of limited reliability. The sensors feature a 40 wt % (≈4 molal) sulfuric acid electrolyte, and carbon working and quasi-reference (QRE) electrodes. We show that the sensor behaves as a truncated transmission line with resistance and capacitance elements varying with humidity. High-amplitude current fluctuations are due to humidity fluctuations, and are charging currents in response to fluctuations in interfacial capacitance. Baseline currents are due to very small differences in the open-circuit electrode potential between working and reference electrodes. We deduce that acid concentration changes in the meniscus within the porous electrode structure, in response to changes in the ambient temperature and humidity, cause both the capacitance fluctuations and the baseline changes. The open-circuit potential differences driving the baseline current variations are in part due to a difference in the liquid junction potential between the QRE and working electrode, dependent on humidity and temperature and caused by a gradient of acid concentration, and in part due to temperature- and acid-concentration-dependent variations in the rate of the potential-determining reactions. Based on the understanding obtained, we demonstrate a simple hardware change that corrects these unwanted errors.

2.
J Biomol Struct Dyn ; : 1-12, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33213303

RESUMEN

In this study, the antimicrobial properties of Plumbago indica root bark against bacterial strains and a fungal strain were investigatedusing the disc diffusion and minimum inhibitory concentration assays. Gas chromatography/mass spectrometry, nuclear magnetic resonance spectrometry, and column chromatography analyses were conducted to identify and isolate the active compounds. A docking study was performed to identify possible interactions between the active compound and DNA gyrase using the Schrödinger Glide docking program. Both methanol extract and the ethyl acetate fraction of the root bark showed significant antimicrobial activity against the gram-positive bacteria than against the gram-negative bacteria and the fungal strain. The active compound was identified as plumbagin. A disc diffusion assay of plumbagin revealed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus. Molecular docking of plumbagin revealed high specificity towards the DNA gyrase binding site with a high fitness score and a minimum energy barrier of -7.651 kcal/mol. These findings indicate that P. indica exhibits significant antimicrobial activity, primarily due to the presence of plumbagin. The specificity of plumbagin toward DNA gyrase in S. aureus indicates the feasibility of utilizing P. indica for developing new drug leads against drug resistant microbial strain. Communicated by Ramaswamy H. Sarma.

3.
Langmuir ; 36(38): 11292-11302, 2020 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-32882136

RESUMEN

We demonstrate the assembly of a compact, gel-like Langmuir-Blodgett film of rods formed by self-assembly of a ß-sheet-forming water-soluble peptide, Ac-IKHLSVN-NH2, at the surface of aqueous electrolytes. We characterize surface pressure hysteresis and demonstrate shear stiffening of the surface caused by area cycling, which we interpret as due to rearrangement and alignment of the rods. We show strong effects of the electrolyte on the assembly of the elementary rods, which can be related to the Hofmeister series and interpreted by effects on the interaction energies mediated by ions and water. Formation of ß-sheet structures and assembly of these into surface-segregated semicrystalline gels was strongly promoted by ammonium sulfate electrolyte. With ammonium sulfate electrolyte as subphase for Langmuir-Blodgett film deposition, shear stiffening by surface area cycling resulted in very compact films on transfer to a substrate.

4.
ACS Appl Mater Interfaces ; 12(35): 39005-39013, 2020 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-32805904

RESUMEN

There is a significant and growing research interest in the isolation of extracellular vesicles (EVs) from large volumes of biological samples and their subsequent concentration into clean and small volumes of buffers, especially for applications in medical diagnostics. Materials that are easily incorporated into simple sampling devices and which allow the release of EVs without the need for auxiliary and hence contaminating reagents are particularly in demand. Herein, we report on the design and fabrication of a flexible, microporous, electrochemically switchable cloth that addresses the key challenges in diagnostic applications of EVs. We demonstrate the utility of our electrochemically switchable substrate for the fast, selective, nondestructive, and efficient capture and subsequent release of EVs. The substrate consists of an electrospun cloth, infused with a conducting polymer and decorated with gold particles. Utilizing gold-sulfur covalent bonding, the electrospun substrates may be functionalized with SH-terminated aptamer probes selective to EV surface proteins. We demonstrate that EVs derived from primary human dermal fibroblast (HDFa) and breast cancer (MCF-7) cell lines are selectively captured with low nonspecific adsorption using an aptamer specific to the CD63 protein expressed on the EV membranes. The specific aptamer-EV interactions enable easy removal of the nonspecifically bound material through washing steps. The conducting polymer component of the cloth provides a means for efficient (>92%) and fast (<5 min) electrochemical release of clean and intact captured EVs by cathodic cleavage of the Au-S bond. We demonstrate successful capture of diluted EVs from a large volume sample and their release into a small volume of clean phosphate-buffered saline buffer. The developed cloth can easily be incorporated into different designs for separation systems and would be adaptable to other biological entities including cells and other EVs. Furthermore, the capture/release capability holds great promise for liquid biopsies if used to targeted disease-specific markers.

5.
Acta Biomater ; 114: 233-243, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32682054

RESUMEN

The effect of installing different lipid chains (C6, C8, C10, and C16) on the N-terminus of an octapeptide derived from the antiparallel ß-interface of the diaminopimelate decarboxylase protein homotetramer has been investigated. Notably, the C8 peptide conjugate assembled into wide twisted nanoribbons and formed hydrogels, which to the best of our knowledge constitutes the first example of a peptide containing an eight carbon alkyl chain that demonstrates these properties, a space typically occupied by peptide amphiphiles with long lipid chains. Furthermore, this self-assembling lipopeptide exhibited pH and temperature stability with shear thinning properties suitable for biomedical applications. Importantly, in this work the application of the polystyrene-based sorbent Diaion™ HP20SS for the simple large-scale purification of self-assembling peptides is presented as an alternative to the use of time-consuming and labor-intensive reverse-phase high-performance liquid chromatography. STATEMENT OF SIGNIFICANCE: Peptides that can self-assemble into defined nanostructures are highly attractive for many biomedical applications given their unique physical and chemical properties. It is recognized that self-assembling peptides derived from naturally occurring proteins offer an unlimited source of functionalities and structures, which are hard to uncover with designed sequences. In this study, we have investigated the effect of installing different lipids chains on the N-terminus of an octapeptide derived from the antiparallel ß-interface of the diaminopimelate decarboxylase protein homo tetramer. We also reported the use of polymeric DiaionⓇ HP20SS beads as an alternative solid support to purify self-assembling peptides.

6.
Molecules ; 25(12)2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32599753

RESUMEN

The increasing prevalence of drug-resistant influenza viruses emphasizes the need for new antiviral countermeasures. The M2 protein of influenza A is a proton-gated, proton-selective ion channel, which is essential for influenza replication and an established antiviral target. However, all currently circulating influenza A virus strains are now resistant to licensed M2-targeting adamantane drugs, primarily due to the widespread prevalence of an M2 variant encoding a serine to asparagine 31 mutation (S31N). To identify new chemical leads that may target M2(S31N), we performed a virtual screen of molecules from two natural product libraries and identified chebulagic acid as a candidate M2(S31N) inhibitor and influenza antiviral. Chebulagic acid selectively restores growth of M2(S31N)-expressing yeast. Molecular modeling also suggests that chebulagic acid hydrolysis fragments preferentially interact with the highly-conserved histidine residue within the pore of M2(S31N) but not adamantane-sensitive M2(S31). In contrast, chebulagic acid inhibits in vitro influenza A replication regardless of M2 sequence, suggesting that it also acts on other influenza targets. Taken together, results implicate chebulagic acid and/or its hydrolysis fragments as new chemical leads for M2(S31N) and influenza-directed antiviral development.

7.
Soft Matter ; 16(28): 6563-6571, 2020 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-32588868

RESUMEN

Increased water solubility and long-range intermolecular ordering have been introduced into the fluorescent organic molecule thiophene-diketopyrrolopyrrole (TDPP) via its conjugation to the octapeptide HEFISTAH, which is derived from the protein-protein ß-interface of the homo-tetramer protein diaminopimelate decarboxylase. The octapeptide, and its TDPP mono- and cross-linked conjugates were synthesised using 9-fluorenylmethoxycarbonyl (Fmoc) based solid-phase peptide synthesis (SPPS). Unlike the unmodified peptide, the resulting mono-linked and cross-linked peptides showed a fibrous morphology and formed hydrogels at 4 wt% in water at neutral pH, but failed to assemble at pH 2 and pH 9. Further peptide characterization showed that the TDPP organic core enhances peptide self-assembly and that both peptides assembled into fibers with a parallel ß-sheet structure. Furthermore, UV-vis spectroscopic analysis suggests that the TDPP molecules form H-type aggregates where the chromophores are likely to be co-facially packed, but rotationally and/or laterally offset from one another. This intermolecular coupling indicates that π-π stacking interactions are highly likely - a favourable sign for charge transport. The enhanced aqueous solubility and self-assembling properties of the TDPP-peptide conjugates allowed the successful preparation of thin films. Atomic force microscopy, X-ray diffraction and UV-vis spectroscopic analysis of these thin films revealed that the hybrid materials retained a fibrous morphology, ß-sheet structures and strong intermolecular coupling between neighbouring TDPP molecules. These results open an exciting avenue for bio-organic materials development, through structural and electronic tuning of the TDPP core.

8.
J Antibiot (Tokyo) ; 73(8): 568-573, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32404991

RESUMEN

Crude extracts of the marine sponge Chelonaplysilla sp. collected in Samoa, that were obtained from the NCI Open Repository (NCS 21903), inhibited Mycobacterium tuberculosis growth. Assay-guided fractionation of the extract led to the isolation and structural elucidation of the known diterpenoid macfarlandin D (1) and three new diterpenoids macfarlandins F (2), G (3), and H (4). Macfarlandin D (1) exhibited potent antimicrobial activity against M. tuberculosis with an MIC of 1.2 ± 0.4 µg mL-1. Macfarlandins F (2), G (3), and H (4) exhibited significantly weaker antitubercular activities, revealing SAR for the macfarlandin antitubercular pharmacophore. The structures of compounds 2, 3, and 4 were elucidated via detailed analysis of NMR and MS data.

9.
Org Lett ; 22(11): 4053-4057, 2020 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-32283033

RESUMEN

Methods for the focused isolation of low-abundance natural products with specific chemical substructures could expand known bioactive chemical diversity for drug discovery. Here we report the combined use of genome mining and an 15N NMR-based screening method for the targeted isolation of the low-abundance piperazic-acid-containing peptides incarnatapeptins A (1) and B (3). Incarnatapeptin B (3) shows in vitro cytotoxicity to LNCaP prostate cancer cells.

10.
Nat Prod Rep ; 37(5): 617-633, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31750842

RESUMEN

Covering: 2000 to 2019The discovery of new natural products that have some combination of unprecedented chemical structures, biological activities of therapeutic interest for urgent medical needs, and new molecular targets provides the fuel that sustains the vitality of natural products chemistry research. Unfortunately, finding these important new compounds is neither routine or trivial and a major challenge is finding effective discovery paradigms. This review presents examples that illustrate the effectiveness of a chemical genetics approach to marine natural product (MNP) discovery that intertwines compound discovery, molecular target identification, and phenotypic response/biological activity. The examples include MNPs that have complex unprecedented structures, new or understudied molecular targets, and potent biological activities of therapeutic interest. A variety of methods to identify molecular targets are also featured.

11.
Pest Manag Sci ; 76(4): 1541-1548, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31696600

RESUMEN

BACKGROUND: Larvae of the diamond back moth (DBM), Plutella xylostella, are destructive cabbage pests causing economic losses worldwide. Continuous application of synthetic pesticides to control this pest has resulted in environmental pollution and resistant pest strains. Thus, there is a crucial need to seek natural alternatives with minimal detrimental effects. This study was designed to investigate the antifeedant activities of endophytic fungi of Cyperus iria and to determine the antifeedant, contact toxicity and oviposition deterrent activities of phyllostine acetate and phyllostine of the endophytic Diaporthe miriciae fungus. RESULTS: Two cyclohexeneoxidediones, phyllostine acetate (1) and phyllostine (2), isolated from an ethyl acetate extract of D. miriciae exhibited strong antifeedant, contact toxicity, and oviposition deterrent activities against P. xylostella. Phyllostine acetate (1) and phyllostine (2) showed feeding deterrent indexes of 100% at 50 µg cm-2 in the no-choice leaf disc assay and 50% feeding deterrence (DC50 ) values of 9 and 4.7 µg cm-2 respectively. The median lethal concentration (LC50 ) values of phyllostine acetate (1) and phyllostine (2) were 4.38 and 6.54 µg/larva in the contact toxicity assay. The oviposition deterrent indexes of the two compounds were 100% for phyllostine acetate (1) and 28.6% for phyllostine (2) at 50 µg cm-2 . CONCLUSION: Phyllostine acetate and phyllostine show promise as compounds for the control of P. xylostella. This study encourages further investigation of endophytic fungi of the family Cyperacea, for the development of natural pest control agents in agriculture. © 2019 Society of Chemical Industry.


Asunto(s)
Mariposas Nocturnas , Oviposición , Acetatos , Animales , Femenino , Hongos , Gentisatos , Larva
12.
Nutr Cancer ; 72(1): 74-87, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31155953

RESUMEN

Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Brassica , Quimioprevención/métodos , Isotiocianatos/administración & dosificación , Próstata/efectos de los fármacos , Neoplasias de la Próstata/prevención & control , Anciano , Anticarcinógenos/administración & dosificación , Disponibilidad Biológica , Biopsia , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Método Doble Ciego , Histona Desacetilasas/sangre , Humanos , Isotiocianatos/orina , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/dietoterapia , Neoplasias de la Próstata/metabolismo , Racemasas y Epimerasas/metabolismo , Productos Vegetales/normas
13.
ACS Sens ; 4(10): 2558-2565, 2019 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-31523961

RESUMEN

The plausibility of data from networks of low-cost measurement devices is a growing and important contentious issue. Informal networks of low-cost devices have particularly come to prominence for air quality monitoring. The contentious point is the believability of data without regular on-site calibration, since this is a specialist task and the costs very quickly become much larger than the cost of installation in the first place. This Sensor Issues suggests that approaches to the problem that involve appropriate use of independent information have the potential to resolve the contention. Ideas are illustrated particularly with reference to low-cost sensor networks for air quality measurement.


Asunto(s)
Monitoreo del Ambiente/instrumentación , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Algoritmos , Calibración , Costos y Análisis de Costo , Monitoreo del Ambiente/economía , Monitoreo del Ambiente/normas , Reproducibilidad de los Resultados
14.
Nat Prod Res ; : 1-4, 2019 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-30964338

RESUMEN

Streptomyces sp. 4054, isolated from marine sediments, produced a new butenolide, mycenolide A (1), along with five known butenolide derivatives (2-6). The structures of the compounds were established based on 1D- and 2D-NMR spectroscopic analysis, circular dichroism, and mass spectrometry data. The antimicrobial activity of the crude extract of the marine bacteria Streptomyces sp. 4054 was evaluated, showing good results against Bacillus subtilis and MRSA.

15.
Cell Chem Biol ; 26(5): 699-710.e6, 2019 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-30880156

RESUMEN

Our inability to effectively "drug" targets such as MYC for therapeutic purposes requires the development of new approaches. We report on the implementation of a phenotype-based assay for monitoring MYC expression in multiple myeloma cells. The open reading frame (ORF) encoding an unstable variant of GFP was engineered immediately downstream of the MYC ORF using CRISPR/Cas9, resulting in co-expression of both proteins from the endogenous MYC locus. Using fluorescence readout as a surrogate for MYC expression, we implemented a pilot screen in which ∼10,000 compounds were prosecuted. Among known MYC expression inhibitors, we identified cardiac glycosides and cytoskeletal disruptors to be quite potent. We demonstrate the power of CRISPR/Cas9 engineering in establishing phenotype-based assays to identify gene expression modulators.


Asunto(s)
Proteínas Proto-Oncogénicas c-myc/genética , Bibliotecas de Moléculas Pequeñas/farmacología , Transcripción Genética/efectos de los fármacos , Bufanólidos/farmacología , Sistemas CRISPR-Cas/genética , Glicósidos Cardíacos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Factor 2 Eucariótico de Iniciación/genética , Factor 2 Eucariótico de Iniciación/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo
16.
J Am Chem Soc ; 141(6): 2201-2204, 2019 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-30698425

RESUMEN

Bacterial capsular polysaccharides are important virulence factors. Capsular polysaccharides from several important Gram-negative pathogens share a conserved glycolipid terminus containing 3-deoxy-ß-d- manno-oct-2-ulosonic acid (ß-Kdo). The ß-Kdo glycosyltransferases responsible for synthesis of this conserved glycolipid belong to a new family of glycosyltransferases that shares little homology with other such enzymes, thereby representing an attractive antivirulence target. Here, we report the development of a fluorescence polarization-based, high-throughput screening assay (FP-tag) for ß-Kdo glycosyltransferases, and use it to identify a class of marine natural products as lead inhibitors. This "FP-tag" assay should be readily adaptable to high-throughput screens of other glycosyltransferases.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Glicosiltransferasas/antagonistas & inhibidores , Química Clic , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Ensayos Analíticos de Alto Rendimiento , Concentración 50 Inhibidora , Azúcares Ácidos/química , Azúcares Ácidos/farmacología
17.
J Antibiot (Tokyo) ; 72(4): 246-251, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30635614

RESUMEN

Culture feeding experiments with [1-13C]-acetate, [2-13C]- acetate, and [1,2-13C]-acetate have shown that the steroid ring B contraction involved in the biogenesis of the unprecedented carbon skeleton of the antibiotic solanioic acid (1) by the fungus Rhizoctonia solani involves cleavage of the C-5/C-6 bond. The study revealed that 9-epi-solanioic acid (4), which spontaneously converts to solanioic acid (1), is also produced by the cultures and it may be the actual natural product.


Asunto(s)
Antibacterianos/biosíntesis , Rhizoctonia/metabolismo , Esteroides/biosíntesis , Vías Biosintéticas , Isótopos de Carbono/metabolismo , Marcaje Isotópico , Rhizoctonia/crecimiento & desarrollo
18.
ACS Pharmacol Transl Sci ; 2(6): 453-467, 2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-32259077

RESUMEN

Inhibition of the androgen receptor (AR) is the mainstay treatment for advanced prostate cancer. Ralaniten (formally EPI-002) prevents AR transcriptional activity by binding to its N-terminal domain (NTD) which is essential for transcriptional activity. Ralaniten acetate (EPI-506) the triacetate pro-drug of ralaniten, remains the only AR-NTD inhibitor to have entered clinical trials (NCT02606123). While well tolerated, the trial was ultimately terminated due to poor pharmacokinetic properties and resulting pill burden. Here we discovered that ralaniten was glucuronidated which resulted in decreased potency. Long-term treatment of prostate cancer cells with ralaniten results in upregulation of UGT2B enzymes with concomitant loss of potency. This has proven to be a useful model with which to facilitate the development of more potent second-generation AR-NTD inhibitors. Glucuronidated metabolites of ralaniten were also detected in the serum of patients in Phase 1 clinical trials. Therefore, we tested an analogue of ralaniten (EPI-045) which was resistant to glucuronidation and demonstrated superiority to ralaniten in our resistant model. These data support that analogues of ralaniten designed to mitigate glucuronidation may optimize clinical responses to AR-NTD inhibitors.

19.
Toxicol Appl Pharmacol ; 364: 97-105, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30582946

RESUMEN

Benzo[a]pyrene (BaP), is a known human carcinogen (International Agency for Research on Cancer (IARC) class 1). The remarkable sensitivity (zepto-attomole 14C in biological samples) of accelerator mass spectrometry (AMS) makes possible, with de minimus risk, pharmacokinetic (PK) analysis following [14C]-BaP micro-dosing of humans. A 46 ng (5 nCi) dose was given thrice to 5 volunteers with minimum 2 weeks between dosing and plasma collected over 72 h. [14C]-BaPeq PK analysis gave plasma Tmax and Cmax values of 1.25 h and 29-82 fg/mL, respectively. PK parameters were assessed by non- compartment and compartment models. Intervals between dosing ranged from 20 to 420 days and had little impact on intra-individual variation. DNA, extracted from peripheral blood mononuclear cells (PBMCs) of 4 volunteers, showed measurable levels (LOD ~ 0.5 adducts/1011 nucleotides) in two individuals 2-3 h post-dose, approximately three orders of magnitude lower than smokers or occupationally-exposed individuals. Little or no DNA binding was detectable at 48-72 h. In volunteers the allelic variants CYP1B1*1/*⁎1, *1/*3 or *3/*3 and GSTM1*0/0 or *1 had no impact on [14C]-BaPeq PK or DNA adduction with this very limited sample. Plasma metabolites over 72 h from two individuals (one CYP1B1*1/*1 and one CYP1B1*3/*3) were analyzed by UPLC-AMS. In both individuals, parent [14C]-BaP was a minor constituent even at the earliest time points and metabolite profiles markedly distinct. AMS, coupled with UPLC, could be used in humans to enhance the accuracy of pharmacokinetics, toxicokinetics and risk assessment of environmental carcinogens.


Asunto(s)
Benzo(a)pireno/farmacocinética , Carcinógenos/farmacocinética , Cromatografía Liquida/métodos , Espectrometría de Masas , Administración Oral , Adulto , Anciano , Benzo(a)pireno/administración & dosificación , Benzo(a)pireno/efectos adversos , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Aductos de ADN/metabolismo , Femenino , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Variantes Farmacogenómicas , Medición de Riesgo , Adulto Joven
20.
J Nat Prod ; 81(10): 2296-2300, 2018 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-30281303

RESUMEN

The new pyrrole-imidazole and pyrrole-guanidine alkaloids 4-debromooroidin (1), 4-debromougibohlin (2), 5-debromougibohlin (3), and 5-bromopalau'amine (4), along with the known hymenidin (5) and (+)-monobromoisophakellin (6), have been isolated from a Dictyonella sp. marine sponge, collected at the Amazon River mouth. The bromine-substitution pattern observed for compounds 1, 2 and 4 is unusual among bromopyrrole alkaloids isolated from marine sponges. The 20S proteasome inhibitory activities of compounds 1-6 have been recorded, with 5-bromopalau'amine (4) being the most active in this series.


Asunto(s)
Poríferos/química , Inhibidores de Proteasoma/química , Inhibidores de Proteasoma/farmacología , Pirroles/química , Pirroles/farmacología , Animales , Brasil , Estructura Molecular , Complejo de la Endopetidasa Proteasomal , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética
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