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1.
Chem Biodivers ; 20(11): e202301013, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37749933

RESUMEN

From the moss Erythrodontium julaceum Paris growing in Vietnam, julacelide (1), a new 3-benzylphthalide, along with methyl orsellinate (2), ethyl orsellinate (3), 4-O-methylhaematommic acid (4), and zeorin (5), were isolated and structurally elucidated. Their chemical structures were elucidated through extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as through comparisons to the existing literature. Compound 4-O-methylhaematommic acid was a new natural product. The absolute configuration of julacelide was defined using time-dependent density functional theory (TDDFT) calculations. Julacelide was evaluated for α-glucosidase inhibition.


Asunto(s)
alfa-Glucosidasas , Estructura Molecular , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , alfa-Glucosidasas/metabolismo , Teoría Funcional de la Densidad
2.
Emerg Infect Dis ; 26(2): 298-306, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31961293

RESUMEN

Hand, foot and mouth disease (HFMD) is an emerging infection with pandemic potential. Knowledge of neutralizing antibody responses among its pathogens is essential to inform vaccine development and epidemiologic research. We used 120 paired-plasma samples collected at enrollment and >7 days after the onset of illness from HFMD patients infected with enterovirus A71 (EV-A71), coxsackievirus A (CVA) 6, CVA10, and CVA16 to study cross neutralization. For homotypic viruses, seropositivity increased from <60% at enrollment to 97%-100% at follow-up, corresponding to seroconversion rates of 57%-93%. Seroconversion for heterotypic viruses was recorded in only 3%-23% of patients. All plasma samples from patients infected with EV-A71 subgenogroup B5 could neutralize the emerging EV-A71 subgenogroup C4. Collectively, our results support previous reports about the potential benefit of EV-A71 vaccine but highlight the necessity of multivalent vaccines to control HFMD.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Enterovirus/inmunología , Enfermedad de Boca, Mano y Pie/epidemiología , Niño , Preescolar , Femenino , Enfermedad de Boca, Mano y Pie/sangre , Enfermedad de Boca, Mano y Pie/prevención & control , Enfermedad de Boca, Mano y Pie/virología , Humanos , Lactante , Recién Nacido , Masculino , Vietnam/epidemiología , Vacunas Virales
3.
Emerg Infect Dis ; 26(1)2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31855527

RESUMEN

In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.


Asunto(s)
Vigilancia de la Población/métodos , Estudios Seroepidemiológicos , Humanos , Vietnam/epidemiología
4.
J Radiol Prot ; 40(4): 1196-1204, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33124601

RESUMEN

A dose calculation for a person who has been in contact with a patient undergoing Nuclear medicine procedures can be performed by using Merged Phantom Tool (MPT). In this study, we are upgrading the MPT to help users easily merge phantoms at any axis and with any angle using the "vector rotation" technique. The segmented structure information of the contact's phantom is also included in the calculation using the GEANT4 "parallel geometry" utility. The calculation is applied to a case of a male cancer patient lying on a bed who has used I-131, and a caregiver standing beside the patient. The equivalent dose to the thyroid of the caregiver is calculated at 0.3, 0.5, 0.8 and 1m away from the patient, as the caregiver is standing near the patient's abdomen, chest and neck area. The results show that the dose to the thyroid of the contact greatly depends on his standing position and that there are clear differences between the results calculated with the point source and those calculated with the patient source. In summary, using activity distributions in the patient's body as well as the right communication circumstance helps to calculate the optimal dose for people who have been in contact with patients.

5.
J Pak Med Assoc ; 69(Suppl 2)(6): S131-S136, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31369543

RESUMEN

OBJECTIVE: Tuberculosis (TB), along with the human immunodeficiency virus, is one of the leading causes of death from infectious diseases. Its prevalence has rendered the treatment of drug-resistant TB a major public health problem that threatens the progress made in TB care and control worldwide. Our objectives were to conduct a systematic review of the cost-effectiveness of treatment for multidrug-resistant and extensively drug-resistant TB (MDR-TB/XDR-TB) and to synthesise available data from scientific research. METHODS: Using English keywords, we searched for papers over reputable databases, such as Scopus, PubMed, Cochrane and Google Scholar, from Jan. 23 to Mar. 23, 2019. RESULTS: The search and screening yielded 13 articles, whose results were extracted and reviewed to draw conclusions on the cost-effectiveness of MDR-TB/XDR-TB treatment. The data extraction table used to cull and categorise the results comprised the characteristics of a given study, as well as its objectives, the perspectives used to guide the investigation, methods and results (outcome, sensitivity analysis). The measured outcome was the incremental cost-effectiveness ratio. CONCLUSIONS: The review indicated that MDR -TB/XDR-TB treatment can be very cost-effective in countries with low to high incomes, regardless of whether minimal or considerable disease burdens exist.


Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/terapia , Hospitalización/economía , Antituberculosos/economía , Análisis Costo-Beneficio , Países en Desarrollo , Técnicas y Procedimientos Diagnósticos/economía , Eficiencia , Tuberculosis Extensivamente Resistente a Drogas/economía , Servicios de Alimentación/economía , Humanos , Años de Vida Ajustados por Calidad de Vida , Transportes/economía , Tuberculosis Resistente a Múltiples Medicamentos/economía , Tuberculosis Resistente a Múltiples Medicamentos/terapia
6.
J Infect Dis ; 216(11): 1371-1379, 2017 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-29029128

RESUMEN

Background: Enterovirus A71 (EV-A71) is the major cause of severe hand, foot, and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam, which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5, and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally. Methods: A total of 752 VP1 gene sequences were analyzed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013, along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to coestimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network. Results: Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity. Conclusion: This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasizing the need for improved EV-A71 surveillance and detailed genetic and antigenic characterization.


Asunto(s)
Enterovirus Humano A/clasificación , Enterovirus Humano A/genética , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/virología , Genotipo , Análisis Espacio-Temporal , Antígenos Virales , Asia/epidemiología , Niño , Preescolar , Brotes de Enfermedades , Enterovirus Humano A/aislamiento & purificación , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/transmisión , Variación Genética , Humanos , Lactante , Recién Nacido , Filogenia , Análisis de Secuencia , Vietnam/epidemiología
8.
Dokl Biochem Biophys ; 464: 294-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26518551
9.
Curr Pharm Teach Learn ; 16(10): 102151, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38996650

RESUMEN

Interprofessional education is acknowledged as an efficacious strategy for fostering collaboration among healthcare professionals, especially in developing countries where interdisciplinarity and cooperation among healthcare practitioners are notably deficient. The present study aimed to investigate the readiness among medical, pharmacy, public health, and nursing faculties for development of an IPE curriculum at a university in Vietnam. Employing a quantitative approach, the revised version of the Readiness for Interprofessional Learning Scale (RIPLS) questionnaire, comprising 19 items, was utilized to gather data from sixty-nine lecturers, including 26 medicine, 23 pharmacy, 11 public health, and 9 nursing faculties. Total scores and subscores (pertaining to teamwork and collaboration, professional identity, and roles and responsibilities) were subjected to comparison using the Kruskal-Wallis and Mann-Whitney U tests. Findings revealed a high level of readiness among all faculty members toward IPE with little difference between each faculty. However, nursing lecturers exhibited a more favorable attitude toward the roles and responsibilities associated with IPE in contrast to their counterparts in the medicine faculty (1.89 ± 1.02 vs 3.15 ± 0.63, p = 0.0048). Further study with deep interview methods should be done to explore the barriers of faculty members as well as of the leadership in developing IPE.


Asunto(s)
Educación Interprofesional , Humanos , Vietnam , Estudios Transversales , Encuestas y Cuestionarios , Educación Interprofesional/métodos , Educación Interprofesional/estadística & datos numéricos , Educación Interprofesional/normas , Universidades/organización & administración , Universidades/estadística & datos numéricos , Masculino , Femenino , Curriculum/tendencias , Curriculum/normas , Adulto , Docentes/psicología , Docentes/estadística & datos numéricos , Empleos en Salud/educación , Relaciones Interprofesionales , Persona de Mediana Edad
10.
Heliyon ; 10(5): e26783, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38434284

RESUMEN

In this study, we investigated the possibility of a photocatalytic system that uses graphene-quantum-dot (GQD)-deposited graphitic carbon nitride (g-C3N4) to treat tetracycline (TC) and other organic compounds generated from an in-situ-recirculatory-aquaculture-system (RAS)-like shrimp farming pond. GQDs were successfully deposited on the exfoliated g-C3N4 base through a hydrothermal treatment. The results showed that the incorporation of GQDs into the g-C3N4 enhanced its porosity without aggregating its mesoporous structure. The GQDs-deposited g-C3N4 photocatalysts revealed sheet-like structures with nanopores on their surface that facilitate photocatalysis. More than 90% of the TC was removed by the photocatalysts under UV-LED irradiation. Low loadings of GQDs over g-C3N4 resulted in a faster and more effective photocatalysis of TC, mainly driven by.O2- radicals. The photocatalysts were also applicable in the degradation of organic compounds with 27% of the total organic compounds (TOC) being removed from the wastewater of a RAS-like shrimp farming pond.

11.
Micromachines (Basel) ; 14(5)2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37241640

RESUMEN

Antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase play important roles in the inhibition of oxidative-damage-related pathological diseases. However, natural antioxidant enzymes face some limitations, including low stability, high cost, and less flexibility. Recently, antioxidant nanozymes have emerged as promising materials to replace natural antioxidant enzymes for their stability, cost savings, and flexible design. The present review firstly discusses the mechanisms of antioxidant nanozymes, focusing on catalase-, superoxide dismutase-, and glutathione peroxidase-like activities. Then, we summarize the main strategies for the manipulation of antioxidant nanozymes based on their size, morphology, composition, surface modification, and modification with a metal-organic framework. Furthermore, the applications of antioxidant nanozymes in medicine and healthcare are also discussed as potential biological applications. In brief, this review provides useful information for the further development of antioxidant nanozymes, offering opportunities to improve current limitations and expand the application of antioxidant nanozymes.

12.
Adv Sci (Weinh) ; 10(16): e2207695, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36991522

RESUMEN

Oxygen evolution reaction (OER) under acidic conditions becomes of significant importance for the practical use of a proton exchange membrane (PEM) water electrolyzer. In particular, maximizing the mass activity of iridium (Ir) is one of the maiden issues. Herein, the authors discover that the Ir-doped calcium copper titanate (CaCu3Ti4O12, CCTO) perovskite exhibits ultrahigh mass activity up to 1000 A gIr -1 for the acidic OER, which is 66 times higher than that of the benchmark catalyst, IrO2 . By substituting Ti with Ir in CCTO, metal-oxygen (M-O) covalency can be significantly increased leading to the reduced energy barrier for charge transfer. Further, highly polarizable CCTO perovskite referred to as "colossal dielectric", possesses low defect formation energy for oxygen vacancy inducing a high number of oxygen vacancies in Ir-doped CCTO (Ir-CCTO). Electron transfer occurs from the oxygen vacancies and Ti to the substituted Ir consequentially resulting in the electron-rich Ir and -deficient Ti sites. Thus, favorable adsorptions of oxygen intermediates can take place at Ti sites while the Ir ensures efficient charge supplies during OER, taking a top position of the volcano plot. Simultaneously, the introduced Ir dopants form nanoclusters at the surface of Ir-CCTO, which can boost catalytic activity for the acidic OER.

13.
RSC Adv ; 12(38): 24511-24517, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36128391

RESUMEN

In this work, a "green" and facile method for synthesis of hierarchical ZSM-5 zeolite was presented by combination of a bio-mesoporogen and a dry gel conversion (DGC) process. ZSM-5 zeolite with high hierarchy factors and excellent mesoporosity was synthesized by adding hydroxypropylmethylcellulose (HPMC), which originated from cellulose biomass, to a zeolitic synthetic gel. The obtained zeolite samples were analyzed by X-ray diffraction (XRD), nitrogen adsorption-desorption (BET) and scanning electron microscopy (SEM) to determine their properties. The influence of crystallization time on the crystallinity of ZSM-5 zeolite was investigated. Moreover, the results showed that HPMC as a pore directing agent is an important factor for the formation of hierarchical zeolite with high mesoporosity. The as-prepared ZSM-5 sample with high pore volume, large surface area and abundant accessible acid sites, which seriously improves diffusion efficiency and catalytic activity, exhibited high catalytic performance in the benzylation reaction.

14.
Nanomaterials (Basel) ; 12(17)2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36080115

RESUMEN

The reaction time, temperature, ratio of precursors, and concentration of sodium citrate are known as the main factors that affect the direct synthesis process of SiO2@Au based on the chemical reaction of HAuCl4 and sodium citrate. Hence, we investigated, in detail, and observed that these factors played a crucial role in determining the shape and size of synthesized nanoparticles. The significant enhancement of the SERS signal corresponding to the fabrication conditions is an existing challenge. Our study results show that the optimal reaction conditions for the fabrication of SiO2@Au are a 1:21 ratio of HAuCl4 to sodium citrate, with an initial concentration of sodium citrate of 4.2 mM, and a reaction time lasting longer than 6 h at a temperature of 80 °C. Under optimal conditions, our synthesis process result is SiO2@Au nanoparticles with a diameter of approximately 350 nm. In particular, the considerable enhancement of Raman intensities of SiO2@Au compared to SiO2 particles was examined.

15.
Drug Deliv ; 29(1): 882-888, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35277106

RESUMEN

PURPOSE: Rheumatoid arthritis, a chronic and progressive inflammation condition in the joints, has significantly reduced the patient quality of life and life expectancy. Crucially, there is no complete therapy for this disease, and the current treatments possess numerous side effects. Thus, novel therapeutic approach is necessary. To that end, this study developed novel silk fibroin in-situ hydrogel containing Sesbania sesban L. extract, a plant with high anti-inflammatory actions that are beneficial for rheumatoid arthritis treatments. METHODS: The hydrogels were manufactured using simple method of spontaneous gelation at different temperature. The gel properties of morphology, gelation time, viscosity, gel strength, stability, drug loading capacity, drug release rate, and in-vitro anti-inflammatory activity were investigated with appropriate methods. RESULTS: The optimal formulation had highly porous structure, with a gelation time of 0.5 h at room temperature and bodily temperature of 37 °C, a viscosity of 2530 ± 50 cP, a gel strength of 1880.14 ± 35.10 g, and a physical stability of >6 months. Moreover, the hydrogel contained the Sesbania sesban L. leaf extract with a total phenolic content of 92.8 ± 8.30 mg GAE/g, and sustained the release rate for >20 days, followed the Higuchi model. Regarding the in-vitro activities, all formulations were nontoxic to the RAW 264.7 cell line and demonstrated comparable anti-inflammatory activity to the free extract, in terms of the NO reduction levels. CONCLUSION: Conclusively, the systems possessed potential properties to be further investigated to become a prospective rheumatoid arthritis treatment.


Asunto(s)
Artritis Reumatoide , Fibroínas , Hidrogeles , Extractos Vegetales/uso terapéutico , Sesbania , Artritis Reumatoide/tratamiento farmacológico , Portadores de Fármacos/química , Fibroínas/química , Humanos , Hidrogeles/química , Extractos Vegetales/administración & dosificación , Estudios Prospectivos , Calidad de Vida , Sesbania/química
16.
Pharmaceutics ; 13(2)2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33670418

RESUMEN

In this work, we chose small intestine submucosa (SIS) as a drug carrier because SIS possesses good biocompatibility, non-immunogenic property and bio-resorbability, and performed electrospinning for preparation of nanofiber sheets (NS). For the preparation of drug-loaded electrospun SIS nanofiber sheets as a drug carrier, we used poly(ε-caprolactone-ran-l-lactide) (PCLA) copolymers to improve the electrospinning performance of SIS. The electrospinning of SIS and PCLA provided the electrospun SIS/PCLA (S/P)-nanofiber sheet (S/P-NS) with adjustable thickness and areas. The electrospun S/P-NS showed different porosities, pore sizes, diameters and tensile strengths depending on the ratios between SIS and PCLA. The electrospun S/P-NS was used as a drug carrier of the dexamethasone (Dex) and silver sulfadiazine (AgS) drug related to anti-inflammation. Dex-loaded S/P-NS and AgS-loaded S/P-NS was successfully fabricated by the electrospinning. In the in vitro and in vivo release, we successfully confirmed the possibility for the sustained release of Dex and AgS from the Dex-S/P-NS and AgS-S/P-NS for three weeks. In addition, the sustained Dex and AgS release suppressed the macrophage infiltration. Collectively, we achieved feasible development of SIS nanofiber sheets for a sustained Dex and AgS delivery system.

17.
Chemosphere ; 282: 131012, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34118630

RESUMEN

The efforts of this study aimed to evaluate the feasibility of the nanotubular halloysites in weathered pegmatites (NaHWP) for removing heavy metals (i.e., Cd2+, Pb2+) from water. Furthermore, two novel intelligent models, such as teaching-learning-based optimization (TLBO)-artificial neural network (ANN), and TLBO-support vector regression (SVR), named as TLBO-ANN and TLBO-SVR models, respectively, were proposed to predict the Cd2+ and Pb2+ absorption efficiencies from water using the NaHWP absorbent. Databases used, including 53 experiments for Pb2+ absorption and 56 experiments for Cd2+ absorption from water, under the catalysis of different conditions, such as initial concentration of Pb2+ and Cd2+, solution pH, adsorbent weight, and contact time. Subsequently, the TLBO-ANN and TLBO-SVR models were developed and applied to predict the efficiencies of Cd2+ and Pb2+ absorption from water, aiming to evaluate the role as well as the effects of different conditions on the absorption efficiencies using the NaHWP absorbent. The standalone ANN and SVM models were also taken into consideration and compared with the proposed hybrid models (i.e., TLBO-ANN and TLBO-SVR). The results showed that the NaHWP detected in a Kaolin mine (Vietnam) with 70% nanotubular halloysites is a potential adsorbent for water treatment to eliminate heavy metals from water. The two novel hybrid models proposed, i.e., TLBO-ANN and TLBO-SVR, also yielded the dominant performances and accuracies in predicting the Cd2+ and Pb2+ absorption efficiencies from water, i.e., RMSE = 1.190 and 1.102, R2 = 0.951 and 0.957, VAF = 94.436 and 95.028 for the TLBO-ANN and TLBO-SVR models, respectively, in predicting the Pb2+ absorption efficiency from water; RMSE = 3.084 and 3.442, R2 = 0.971 and 0.965, VAF = 96.499 and 96.415 for the TLBO-ANN and TLBO-SVR models, respectively, in predicting the Cd2+ absorption efficiency from water. Furthermore, the validation results also demonstrated these findings in practice through 23 experiments with the accuracies of 98.3% and 98.37% for the TLBO-ANN and TLBO-SVR models, respectively, in predicting the Pb2+ absorption efficiency from water; the accuracies of 98.3% and 97.46% for the TLBO-ANN and TLBO-SVR models, respectively, in predicting the Cd2+ absorption efficiency from water. Besides, solution pH was evaluated as the most critical parameter that can be adjusted to enhance the performance of the absorption of the heavy metals in this study. By using the NaHWP absorbent and the novel proposed intelligent models developed, heavy metals can be eliminated entirely from water, providing pure water/clean freshwater without any risk of adverse health effects for the short term or long term.


Asunto(s)
Inteligencia Artificial , Metales Pesados , Algoritmos , Arcilla , Humanos , Metales Pesados/análisis , Agua
18.
Chemosphere ; 268: 129329, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33360937

RESUMEN

This study develops a method to reuse aquaculture wastewater and sediment from a catfish pond in order to increase agricultural productivity and protect the environment. Material flow analysis (MFA) is a central concept of this study that involves collecting catfish pond wastewater (CPW) and reusing it to irrigate five water spinach (Ipomoea aquatic) ponds before discharging it into a river. Typically, catfish pond sediment (CPS) was collected and composted to produce organic fertilizer for cornfields. The results revealed that pollutant removal efficiency of wastewater from CPW (by using water spinach) were total organic carbon (TOC) = 38.78%, nitrogen (N) = 27.07%, phosphorous (P) = 58.42%, and potassium (K) = 28.64%. By adding 20 tons of CPS compost per hectare of the cornfield, the corn yield boosted 15% compared to the control field. In addition, the water spinach grew and developed well in the medium of wastewater from the fish pond. Altogether, the results illustrate that catfish pond wastewater and sediment can act as organic fertilizers for crops meanwhile reduce environmental pollution from its reuse.


Asunto(s)
Ipomoea , Aguas Residuales , Animales , Acuicultura , Estanques , Aguas Residuales/análisis , Zea mays
19.
Am J Chin Med ; 49(6): 1437-1448, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34247560

RESUMEN

Linalool, a major odorous constituent in essential oils extracted from lavender, is known to have a wide range of physiological effects on humans including pain management. The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is involved in transmission of orofacial nociceptive responses through thin myelinated A[Formula: see text] and unmyelinated C primary afferent fibers. Up to date, the orofacial antinociceptive mechanism of linalool concerning SG neurons of the Vc has not been completely clarified yet. To fill this knowledge gap, whole-cell patch-clamp technique was used in this study to examine how linalool acted on SG neurons of the Vc in mice. Under a high chloride pipette solution, non-desensitizing and repeatable linalool-induced inward currents were preserved in the presence of tetrodotoxin (a voltage-gated Na[Formula: see text]channel blocker), CNQX (a non-NMDA glutamate receptor antagonist), and DL-AP5 (an NMDA receptor antagonist). However, linalool-induced inward currents were partially suppressed by picrotoxin (a GABA[Formula: see text] receptor antagonist) or strychnine (a glycine receptor antagonist). These responses were almost blocked in the presence of picrotoxin and strychnine. It was also found that linalool exhibited potentiation with GABA- and glycine-induced responses. Taken together, these data show that linalool has GABA- and glycine-mimetic effects, suggesting that it can be a promising target molecule for orofacial pain management by activating inhibitory neurotransmission in the SG area of the Vc.


Asunto(s)
Monoterpenos Acíclicos/farmacología , Glicina/metabolismo , Manejo del Dolor/métodos , Sustancia Gelatinosa/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Núcleo Caudal del Trigémino/efectos de los fármacos , Ácido gamma-Aminobutírico/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones
20.
Med Chem ; 17(7): 732-749, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32310052

RESUMEN

BACKGROUND: The target-based approach to drug discovery currently attracts a great deal of interest from medicinal chemists in anticancer drug discovery and development. Histone deacetylase (HDAC) inhibitors represent an extensive class of targeted anti-cancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as vorinostat and belinostat. AIMS: This study aims at developing novel HDAC inhibitors bearing conjugated quinazolinone scaffolds with potential cytotoxicity against different cancer cell lines. METHODS: A series of novel N-hydroxyheptanamides incorporating conjugated 6-hydroxy-2 methylquinazolin- 4(3H)-ones (15a-l) was designed, synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines, including HepG-2, MCF-7 and SKLu-1. Molecular simulations were finally performed to gain more insight into the structureactivity relationships. RESULTS: It was found that among novel conjugated quinazolinone-based hydroxamic acids synthesized, compounds 15a, 15c and 15f were the most potent, both in terms of HDAC inhibition and cytotoxicity. Especially, compound 15f displayed up to nearly 4-fold more potent than SAHA (vorinostat) in terms of cytotoxicity against MCF-7 cell line with IC50 value of 1.86 µM, and HDAC inhibition with IC50 value of 6.36 µM. Docking experiments on HDAC2 isozyme showed that these compounds bound to HDAC2 with binding affinities ranging from -10.08 to -14.93 kcal/mol compared to SAHA (-15.84 kcal/mol). It was also found in this research that most of the target compounds seemed to be more cytotoxic toward SKLu-1than MCF-7 and HepG-2. CONCLUSION: The resesrch results suggest that some hydroxamic acids could emerge for further evaluation and the results are well served as basics for further design of more potent HDAC inhibitors and antitumor agents.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Diseño de Fármacos , Ácidos Hidroxámicos/síntesis química , Ácidos Hidroxámicos/farmacología , Quinazolinonas/química , Antineoplásicos/química , Línea Celular Tumoral , Técnicas de Química Sintética , Humanos , Ácidos Hidroxámicos/química
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