RESUMEN

Non-heme iron oxygenases constitute a versatile enzyme family that is crucial for incorporating molecular oxygen into diverse biomolecules. Despite their importance, only a limited number of these enzymes have been structurally and functionally characterized. Surprisingly, there remains a significant gap in understanding how these enzymes utilize a typical architecture and reaction mechanism to catalyze a wide range of reactions. Improving our understanding of these catalysts holds promise for advancing both fundamental enzymology and practical applications. This chapter aims to outline methods for heterologous expression, enzyme preparation, in vitro enzyme assays, and crystallization of biphenyl dioxygenase, phthalate dioxygenase and terephthalate dioxygenase. These enzymes catalyze the dihydroxylation of biphenyl, phthalate and terephthalate molecules, serving as a model for functional and structural analysis of other non-heme iron oxygenases.

Asunto(s)

Compuestos de Bifenilo , Cristalización , Ácidos Ftálicos , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismo , Compuestos de Bifenilo/química , Cinética , Cristalización/métodos , Dioxigenasas/química , Dioxigenasas/metabolismo , Dioxigenasas/genética , Hierro/química , Hierro/metabolismo , Cristalografía por Rayos X/métodos , Pruebas de Enzimas/métodos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Oxigenasas

RESUMEN

Microplastics (MPs) are particles between 1 µm and 5 mm in size, originating mainly from poor solid waste and effluent management, that can reach water bodies from various sources. In freshwater environments, the occurrence, distribution, and characterization of this new class of pollutants are still little explored, especially in Brazil. The aim of this study was to assess the occurrence of MPs, as well as the presence and concentration of polychlorinated biphenyls (PCBs) sorbed to these particles in the surface waters of the Tietê River - SP. Surface water samples were collected in duplicate during the dry and wet seasons. The identification and characterization of the MPs was carried out through visual inspection and the chemical identity of the particles was verified using Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR). For the analysis of PCBs adsorbed to the MPs, the sample extracts were analyzed by gas chromatography coupled with mass spectrometry (GC-MS). The MPs were found in concentrations ranging from 6.67 to 1530 particles m-3, with a predominance of the polymers polyethylene (PE, with 58.17 %) and polypropylene (PP, with 23.53 %). The main morphological categories identified were fragments (56.63 %), fibers (28.42 %), and transparent films (13.06 %). Higher abundances of PCBs were observed in the lower size range, between 0.106 and 0.35 mm. The total concentrations of PCBs in MPs ranged from 20.53 to 133.12 ng g-1. The results obtained here are relevant for understanding the dynamics and level of contamination of MPs and organic pollutants sorbed to these particles in the Tietê River, as well as helping with mitigation measures for the restoration and preservation of this ecosystem.

RESUMEN

An efficient metal-free, triflic acid-promoted intramolecular Friedel-Crafts-type carbocyclization of alkenylated biphenyl derivatives is discussed. This method provides an elegant route for the construction of 9,10-dihydrophenanthrenes of biological significance in good to excellent yields. The carbocyclization reaction is likely to proceeds via activation of terminal C[bond, double bond]C bond of alkenylated biphenyl derivatives followed by subsequent aromatic electrophilic substitution to give desired carbocyclic products. Single crystal X-ray diffraction analysis of compound 10d revealed that the crystals are packed in AB-AB layer packing, where the molecules are aligned in anti-parallel fashion. Notably, all of the synthesized 9,10-dihydrophenanthrenes exhibited blue to greenish yellow fluorescence with λ max = 418-481 nm range. The stokes shift, quantum yield and optical band gap of tricyclic products were computed using their absorption and emission spectra. A significant positive solvatochromic effect was observed for 9,10-dihydrophenanthrene derivative 10l, which is a characteristic of ICT interactions.

RESUMEN

Polychlorinated biphenyls (PCBs) and dioxin are persistent endocrine disrupting chemicals (EDCs) and have been associated with an increased risk of metabolic syndrome (MetS). The aim of this systematic review and meta-analysis was to assess the associations of PCBs and dioxin with MetS and its risk factors, including obesity, hypertriglyceridaemia (HTG), hypertension (HTN) and diabetes mellitus (DM). We searched three electronic databases for epidemiological studies concerning PCBs and dioxin with MetS published up to the end of 2023. Meta-analysis was performed for MetS itself and each of the MetS risks based on a random-effects meta-analysis model, and odds ratios (ORs) with 95% confidence intervals (CIs) were obtained. Publication bias was assessed based on Egger's test. Eleven studies were included from three databases up to 2023. There were 40,528 participants aged 18-89, where 18-100% of them were males, included in our meta-analysis. The meta-analysis results showed a strong association between PCB exposure and DM (OR = 3.593, 95% CI 2.566, 5.031), while most of the risk factors for MetS, including obesity (OR = 1.875, 95% CI 0.883, 3.979), HTN (OR = 1.335, 95% CI 0.902, 1.976) and HTG (OR = 1.611, 95% CI 0.981, 2.643), were weakly associated with PCB. Furthermore, both PCBs (OR = 1.162, 95% CI 0.994, 1.357) and dioxin (OR = 2.742, 95% CI 1.936, 3.883) were found to be weakly and strongly associated with MetS, respectively. Meta-regression analysis showed that DM in the Asian population is associated with PCB exposure, while HTG in the Northern American population is associated with PCB exposure. Our meta-analysis has demonstrated a strong relationship between DM and PCBs, while the relationship between PCBs with MetS and other risk factors is less pronounced. Additionally, MetS is weakly associated with dioxin exposure. To improve primary care outcomes, healthcare providers should consider incorporating the assessment of patients' risk of exposure to PCBs and dioxins into their evaluation procedures for more targeted medical interventions.

Asunto(s)

Dioxinas , Síndrome Metabólico , Bifenilos Policlorados , Humanos , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/epidemiología , Bifenilos Policlorados/efectos adversos , Dioxinas/efectos adversos , Factores de Riesgo , Femenino , Masculino , Adulto , Obesidad/inducido químicamente , Persona de Mediana Edad , Exposición a Riesgos Ambientales/efectos adversos , Anciano , Adolescente , Hipertensión/inducido químicamente , Hipertensión/epidemiología

RESUMEN

Elevated airborne PCB levels in older schools are concerning due to their health impacts, including cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular issues, neurodevelopmental diseases, and diabetes. During a four-week inhalation exposure to PCB52, an air pollutant commonly found in school environments, adolescent rats exhibited notable presence of PCB52 and its hydroxylated forms in their livers, alongside changes in gene expression. Female rats exhibited more pronounced changes in gene expression compared to males, particularly in fatty acid synthesis genes regulated by the transcription factor SREBP1. In vitro studies with human liver cells showed that the hydroxylated metabolite of PCB52, 4-OH-PCB52, but not the parent compound, upregulated genes involved in fatty acid biosynthesis similar to in vivo exposure. These findings highlight the sex-specific effects of PCB52 exposure on livers, particularly in females, suggesting a potential pathway for increased MASLD susceptibility.

Asunto(s)

Ácidos Grasos , Exposición por Inhalación , Hígado , Bifenilos Policlorados , Regulación hacia Arriba , Animales , Femenino , Bifenilos Policlorados/toxicidad , Hígado/metabolismo , Hígado/efectos de los fármacos , Masculino , Regulación hacia Arriba/efectos de los fármacos , Ácidos Grasos/metabolismo , Humanos , Contaminantes Atmosféricos/toxicidad , Ratas , Ratas Sprague-Dawley , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo

RESUMEN

The title compound, [Re(C17H22N3O2S)(CO)3] is a net neutral fac-Re(I)(CO)3 complex of the 4-methyl-biphenyl sulfonamide derivatized di-ethyl-enetri-amine ligand. The NNN-donor monoanionic ligand coordinates with the Re core in tridentate fashion, establishing an inner coordination sphere resulting in a net neutral complex. The complex possesses pseudo-octa-hedral geometry where one face of the octa-hedron is occupied by three carbonyl ligands and the other faces are occupied by one sp 2 nitro-gen atom of the sulfonamide group and two sp 3 nitro-gen atoms of the dien backbone. The Re-Nsp 2 bond distance, 2.173 (4) Å, is shorter than the Re-Nsp 3 bond distances, 2.217 (5) and 2.228 (6) Å, and is similar to the range reported for typical Re-Nsp 2 bond lengths (2.14 to 2.18 Å).

RESUMEN

The scope of this study was to apply advances in materials science, specifically the use of organosilicate nanoparticles as a high surface area platform for passive sampling of chemicals or pre-concentration for active sensing in multiple-phase complex environmental media. We have developed a novel nanoporous organosilicate (NPO) film as an extraction phase and proof of concept for application in adsorbing hydrophobic compounds in water and sediment. We characterized the NPO film properties and provided optimization for synthesis and coatings in order to apply the technology in environmental media. NPO films in this study had a very high surface area, up to 1325 m2/g due to the high level of mesoporosity in the film. The potential application of the NPO film as a sorbent phase for sensors or passive samplers was evaluated using a model hydrophobic chemical, polychlorinated biphenyls (PCB), in water and sediment. Sorption of PCB to this porous high surface area nanoparticle platform was highly correlated with the bioavailable fraction of PCB measured using whole sediment chemistry, porewater chemistry determined by solid-phase microextraction fiber methods, and the Lumbriculus variegatus bioaccumulation bioassay. The surface-modified NPO films in this study were found to highly sorb chemicals with a log octanol-water partition coefficient (Kow) greater than four; however, surface modification of these particles would be required for application to other chemicals.

Asunto(s)

Sedimentos Geológicos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas , Nanopartículas/química , Agua/química , Bifenilos Policlorados/análisis , Contaminantes Químicos del Agua/análisis , Compuestos de Organosilicio/química , Adsorción , Propiedades de Superficie

RESUMEN

Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki-Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98-100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.

Asunto(s)

Herbicidas , Pirimidinas , Herbicidas/química , Herbicidas/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Acetolactato Sintasa/antagonistas & inhibidores , Acetolactato Sintasa/metabolismo , Acetolactato Sintasa/química , Compuestos de Bifenilo/química , Compuestos de Bifenilo/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Malezas/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular

RESUMEN

With the popularization of 5G technology and artificial intelligence, thermally conductive epoxies with self-healing ability will be widely used in flexible electronic materials. Although many compounds containing both performances have been synthesized, there is little systematic theory to explain the coordination mechanism. In this paper, alkyl chains of different lengths were introduced to epoxies to discuss the thermally conductive, the self-healing performance, and the synergistic effect. A series of electronic-grade biphenyl epoxies (4,4'-bis(oxiran-2-ylmethoxy)-1,1'-biphenyl (1), 4,4'-bis(2-(oxiran-2-yl)ethoxy)-1,1'-biphenyl (2), 4,4'-bis(3-(oxiran-2-yl)propoxy)-1,1'-biphenyl (3), and 4,4'-bis(4-(oxiran-2-yl)butoxy)-1,1'-biphenyl (4) were synthesized and characterized. Furthermore, they were cured with decanedioic acid to produce polymers. Results showed that alkyl chains can both affect the two properties, and the epoxies suitable for specific application scenarios can be prepared by adjusting the length of alkyl chains. In terms of thermal conductivity, compound 1 was a most promising material. However, compound 4 was expected to be utilized in flexible electronic devices because of its acceptable thermal conductivity, self-healing ability, transparency, and flexibility.

RESUMEN

The chemistry of quinone methides formed in situ has been flourishing in recent years. In sharp contrast, the development and utilization of biphenyl quinone methides are rare. In this study, we achieved a remote stereocontrolled 1,12-conjugate addition of biphenyl quinone methides formed in situ for the first time. In the presence of a suitable chiral phosphoric acid, alkynyl biphenyl quinone methides were generated from α-[4-(4-hydroxyphenyl)phenyl]propargyl alcohols, followed by enantioselective 1,12-conjugate addition with indole-2-carboxylates. The strategy enabled the alcohols to serve as efficient allenylation reagents, providing practical access to a broad range of axially chiral allenes bearing a (1,1'-biphenyl)-4-ol unit, which were previously less accessible. Combined with control experiments, density functional theory calculations shed light on the reaction mechanism, indicating that enantioselectivity originates from the nucleophilic addition of alkynyl biphenyl quinone methides. Notably, not only the presence of biphenyl quinone methides as versatile intermediates was confirmed but also organocatalytic enantioselective 1,12-addition was established.

RESUMEN

INTRODUCTION: Endocrine disruptors are compounds of manmade origin able to interfere with the endocrine system and constitute an important environmental concern. Indeed, detrimental effects on thyroid physiology and functioning have been described. Differences exist in the susceptibility of human sexes to the incidence of thyroid disorders, like autoimmune diseases or cancer. METHODS: To study how different hormonal environments impact the thyroid response to endocrine disruptors, we exposed human embryonic stem cell-derived thyroid organoids to physiological concentrations of sex hormones resembling the serum levels of human females post-ovulation or males of reproductive age for three days. Afterwards, we added 10 µM benzo[a]pyrene or PCB153 for 24 h and analyzed the transcriptome changes via single-cell RNA sequencing with differential gene expression and gene ontology analysis. RESULTS: The sex hormones receptors genes AR, ESR1, ESR2 and PGR were expressed at low levels. Among the thyroid markers, only TG resulted downregulated by benzo[a]pyrene or benzo[a]pyrene with the "male" hormones mix. Both hormone mixtures and benzo[a]pyrene alone upregulated ribosomal genes and genes involved in oxidative phosphorylation, while their combination decreased the expression compared to benzo[a]pyrene alone. The "male" mix and benzo[a]pyrene, alone or in combination, upregulated genes involved in lipid transport and metabolism (APOA1, APOC3, APOA4, FABP1, FABP2, FABP6). The combination of "male" hormones and benzo[a]pyrene induced also genes involved in inflammation and NFkB targets. Benzo[a]pyrene upregulated CYP1A1, CYP1B1 and NQO1 irrespective of the hormonal context. The induction was stronger in the "female" mix. Benzo[a]pyrene alone upregulated genes involved in cell cycle regulation, response to reactive oxygen species and apoptosis. PCB153 had a modest effect in presence of "male" hormones, while we did not observe any changes with the "female" mix. CONCLUSION: This work shows how single cell transcriptomics can be applied to selectively study the in vitro effects of endocrine disrupters and their interaction with different hormonal contexts.

Asunto(s)

Benzo(a)pireno , Disruptores Endocrinos , Hormonas Esteroides Gonadales , Bifenilos Policlorados , Glándula Tiroides , Transcriptoma , Humanos , Benzo(a)pireno/toxicidad , Bifenilos Policlorados/toxicidad , Disruptores Endocrinos/toxicidad , Transcriptoma/efectos de los fármacos , Glándula Tiroides/efectos de los fármacos , Femenino , Masculino , Análisis de la Célula Individual , Células Madre Embrionarias Humanas/efectos de los fármacos , Células Madre Embrionarias Humanas/metabolismo

RESUMEN

INTRODUCTION: Allosteric inhibition of EGFR Tyrosine Kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies. METHOD: A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy. Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. RESULT: All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity. CONCLUSION: Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

RESUMEN

Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.

Asunto(s)

Antagonistas de Receptores Androgénicos , Antineoplásicos , Benzamidas , Compuestos de Bifenilo , Proliferación Celular , Resistencia a Antineoplásicos , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Receptores Androgénicos , Humanos , Masculino , Benzamidas/farmacología , Benzamidas/química , Benzamidas/síntesis química , Nitrilos/química , Nitrilos/farmacología , Feniltiohidantoína/farmacología , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/química , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/antagonistas & inhibidores , Receptores Androgénicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Estructura Molecular , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/química , Antagonistas de Receptores Androgénicos/síntesis química , Antagonistas de Receptores Androgénicos/uso terapéutico , Descubrimiento de Drogas , Ensayos de Selección de Medicamentos Antitumorales , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral

RESUMEN

In the crystal of the title compound, C18H14O10·2H2O, the arene rings of the biphenyl moiety are tilted at an angle of 24.3 (1)°, while the planes passing through the carboxyl groups are rotated at angles of 8.6 (1) and 7.7 (1)° out of the plane of the benzene ring to which they are attached. The crystal structure is essentially stabilized by O-H⋯O bonds. Here, the carboxyl groups of neighbouring host mol-ecules are connected by cyclic R 2 2(8) synthons, leading to the formation of a three-dimensional network. The water mol-ecules in turn form helical supra-molecular strands running in the direction of the crystallographic c-axis (chain-like water clusters). The second H atom of each water mol-ecule provides a link to a meth-oxy O atom of the host mol-ecule. A Hirshfeld surface analysis was performed to qu-antify the contributions of the different inter-molecular inter-actions, indicating that the most important contributions to the crystal packing are from H⋯O/O⋯H (37.0%), H⋯H (26.3%), H⋯C/C⋯H (18.5%) and C⋯O/O⋯C (9.5%) inter-actions.

RESUMEN

Background: Although the causes of attention-deficit/hyperactivity disorder (ADHD) and autism have not been identified, exposure to endocrine-disrupting chemicals, such as polybrominated biphenyl (PBB), during fetal development and early life has been suspected to impact neurological development. This study aims to investigate the association between prenatal and early life exposure to PBB and the development of ADHD and autism later in life. Methods: Data from the Michigan PBB Registry, a cohort of Michigan residents who had been exposed to PBB in a mass contamination event in 1973, was leveraged for this nested case-control analysis among two distinct samples: (1) Those who self-reported ADHD or autism diagnosis, and (2) mothers who reported their child's ADHD or autism diagnosis. PBB exposure was measured in participants of the PBB Registry, and the mother's PBB level was used in mother-reported analyses. Cases were matched with controls by sex and year of birth. Conditional logistic regression models were used to estimate the association between PBB level and case status. Results: PBB levels were higher among those who were exposed in early life compared with those exposed in utero (geometric mean: 0.300 ng/ml vs. 0.016 ng/ml). Among women in this cohort, a higher than expected proportion of self-reported ADHD diagnosis (11.11%), compared with population estimates. PBB was not associated with ADHD or autism in either self-reported or mother-reported analyses. Conclusions: This study adds to the sparse literature about prenatal and early life exposure to PBB-153 and ADHD and autism. Future studies should examine potential effect modification by sex.

RESUMEN

Resuscitation promoting factors (Rpfs), known for their anti-dormancy cytokine properties, have been extensively investigated in the medical field. Although the Rpf from Micrococcus luteus has been successfully utilized to resuscitate and stimulate microbial populations for the degradation of polychlorinated biphenyls (PCBs), the presence of indigenous Rpf homologs in PCB-contaminated soils has not been established. In this study, the distribution characteristics of rpf-like genes and indigenous strain capable of producing Rpf in PCB-contaminated soils were explored. The results revealed the widespread presence of Rpf-like domains and their associated genes, particularly in close association with heavy metals and PCBs. The rpf-like genes were predominantly found in Proteobacteria and displayed a positive correlation with genes involved in PCB degradation and viable but non-culturable (VBNC) formation. Notably, the recombinant Rpf-Ac protein derived from the indigenous strain Achromobacter sp. HR2 exhibited muralytic activity and demonstrated significant efficacy in resuscitating the growth of VBNC cells, while also stimulating the growth of normal cells. These findings shed light on the prevalent presence of Rpf homologs in PCB-contaminated soils and their potential to resuscitate functional populations in the VBNC state, thereby enhancing in situ bioremediation.

Asunto(s)

Bifenilos Policlorados , Biodegradación Ambiental , Suelo

RESUMEN

INTRODUCTION: Gomisin is a natural dibenzo cyclooctene lignan, which is mainly derived from the family Magnoliaceae. It has anti-inflammatory, antioxidant, anti-tumor, anti-aging, and hypoglycemic effects. Gomisins play important roles as medicines, nutraceuticals, food additives, and cosmetics. OBJECTIVE: The objective of this study is to establish a micellar electrokinetic chromatography (MEKC) method for simultaneous separation and determination of seven biphenyl cyclooctene lignans (Gomisin D, E, G, H, J, N, and O) in Schisandra chinensis and its preparations. METHODS: The method was optimized by studying the effects of the main parameters on the separation. The method has been validated and successfully applied to the determination of seven Gomisins in S. chinensis and its preparations. RESULTS: In the separation system, the running buffer was composed of 20 mM Na2HPO4, 8.0 mM sodium dodecyl sulfate (SDS), 11% (v/v) methanol, and 6.0% (v/v) ethanol. A diode array detector was used with a detection wavelength of 230 nm, a separation voltage of 17 kV, and an operating temperature of 25°C. Under this condition, the seven analytes were separated at baseline within 20 min, and a good linear relationship was obtained with correlation coefficient ranging from 0.9919 to 0.9992. The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) ranged from 0.8 to 0.9 µg/mL and from 2.6 to 3.0 µg/mL, respectively. The recovery rate was between 99.1% and 102.5%. CONCLUSION: The experimental results indicated that this method is suitable for the separation and determination of seven Schisandra biphenyl cyclooctene lignan compounds in real samples. At the same time, it provides an effective reference for the quality control of S. chinensis and its preparations.

Asunto(s)

Cromatografía Capilar Electrocinética Micelar , Ciclooctanos , Lignanos , Schisandra , Solventes , Lignanos/análisis , Schisandra/química , Cromatografía Capilar Electrocinética Micelar/métodos , Solventes/química , Ciclooctanos/análisis , Ciclooctanos/química , Reproducibilidad de los Resultados , Límite de Detección , Compuestos de Bifenilo/química

RESUMEN

The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the meta or para position of the biphenyl ring categorized into two distinct groups: [4,3']biphenylaminoquinoline-substituted and [3,3']biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure-activity relationship. Furthermore, we determined the IC50 values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3']biphenylaminoquinoline derivative 7j displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC50 values of 1.05 µM, 0.98 µM, 0.38 µM, and 0.17 µM, respectively. This highly promising outcome underscores the potential of [3,3']biphenylaminoquinoline 7j for further investigation as a prospective anticancer agent in future research endeavors.

Asunto(s)

Antineoplásicos , Compuestos de Bifenilo , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Relación Estructura-Actividad , Línea Celular Tumoral , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/química , Ensayos de Selección de Medicamentos Antitumorales , Aminoquinolinas/química , Aminoquinolinas/farmacología , Aminoquinolinas/síntesis química , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos

RESUMEN

Pollutants produced by cremation furnaces have gradually caused concern because of the increasing rate of cremation around the world. In this study, the levels, patterns, and emission factors of unintentional persistent organic pollutants (UPOPs) from cremation were investigated. The toxic equivalent (TEQ) concentrations (11 % O2 normalized) of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in flue gas ranged from 0.036 to 22 ng TEQ/Nm3, while the levels of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) in flue gas samples ranged from 0.0023 to 1.2 ng TEQ/Nm3 and 0.17-44 pg TEQ/Nm3, respectively. The average concentrations of UPOPs in flue gas from car-type furnaces were higher than those from flat-panel furnaces. Secondary chambers and air pollution control devices were effective for controlling UPOPs emissions. However, heat exchangers were not as effective for reducing UPOPs emissions. It was observed that the UPOPs profiles exhibited dissimilarities between fly ash and flue gas samples. HxCDF, OCDD, and PeCDF were the dominant homologs of PCDD/Fs in flue gas, while HxCDF, PeCDF, and HpCDF were the dominant homologs in fly ash. The fractions of MoCBs and MoCNs in fly ash were higher than those in flue gas. Finally, we conducted an assessment of the global emissions of UPOPs from cremation in the years of 2019 and 2021. The total emission of UPOPs in 47 countries was estimated at 239 g TEQ in 2021, which was during the peak period of the COVID-19 pandemic worldwide. The emissions in 2021 increased by approximately 24 % compared to 2019, with the impact of COVID-19 being a significant factor that cannot be disregarded.

Asunto(s)

Contaminantes Atmosféricos , Cremación , Monitoreo del Ambiente , Contaminantes Orgánicos Persistentes , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Dibenzodioxinas Policloradas/análisis , Bifenilos Policlorados/análisis , Incineración , Dibenzofuranos Policlorados/análisis , Contaminación del Aire/estadística & datos numéricos

RESUMEN

Identification of estrogen receptor (ER) agonists among environmental toxicants is essential for assessing the potential impact of toxicants on human health. Using 2D autocorrelation descriptors as predictor variables, two binary logistic regression models were developed to identify active ER agonists among hydroxylated polychlorinated biphenyls (OH-PCBs). The classifications made by the two models on the training set compounds resulted in accuracy, sensitivity and specificity of 95.9 %, 93.9 % and 97.6 % for ERα dataset and 91.9 %, 90.9 % and 92.7 % for ERß dataset. The areas under the ROC curves, constructed with the training set data, were found to be 0.985 and 0.987 for the two models. Predictions made by models I and II correctly classified 84.0 % and 88.0 % of the test set compounds and 89.8 % and 85.8% of the cross-validation set compounds respectively. The two classification-based QSAR models proposed in this paper are considered robust and reliable for rapid identification of ERα and ERß agonists among OH-PCB congeners.