RESUMEN
Seventeen novel 2-(5-amino-1-(substituted sulfonyl)-1H-1,2,4-triazol-3-ylthio)-6- isopropyl-4,4-dimethyl-3,4-dihydronaphthalen-1(2H)-one compounds were synthesized from the abundant and naturally renewable longifolene and their structures were confirmed by FT-IR, NMR, and ESI-MS. The in vitro cytotoxicity of the synthesized compounds was evaluated by standard MTT assay against five human cancer cell lines, i.e., T-24, MCF-7, HepG2, A549, and HT-29. As a result, compounds 6d, 6g, and 6h exhibited better and more broad-spectrum anticancer activity against almost all the tested cancer cell lines than that of the positive control, 5-FU. Some intriguing structure-activity relationships were found and are discussed herein by theoretical calculation.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Sesquiterpenos/farmacología , Tetralonas/farmacología , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Neoplasias/patología , Sesquiterpenos/síntesis química , Sesquiterpenos/química , Espectrometría de Masa por Ionización de Electrospray , Espectroscopía Infrarroja por Transformada de Fourier , Tetralonas/síntesis química , Tetralonas/química , Triazoles/síntesis química , Triazoles/químicaRESUMEN
The Wnt/ß-catenin pathway plays a vital role in initiating and sustaining hepatocellular carcinoma (HCC). However, few studies have investigated polymorphisms in the Wnt/ß-catenin signaling pathway genes in the Chinese Han population. The aim of the present retrospective study was to investigate the correlations between polymorphisms of the Wnt/ß-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression.Twenty tagging single nucleotide polymorphisms were chosen from HapMap data and genotyped in 320 patients with HCC, 320 chronic hepatitis B virus (HBV)-infected patients without HCC (N-HCC, including 95 liver cirrhosis, 164 chronic hepatitis B, and 61 asymptomatic HBV carriers), and 320 healthy controls. Associations between polymorphisms in the 2 Wnt/ß-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression were investigated.Genotype AA (Pâ=â0.002, odds ratio [OR]â=â2.524) and allele A (Pâ=â0.0003, ORâ=â1.613) of the WNT2 rs4730775 polymorphism were associated with HCC susceptibility compared with healthy controls. Genotype GA (Pâ=â0.001, ORâ=â0.567) and allele A (Pâ=â0.002, ORâ=â0.652) of rs3864004, and genotype AG (Pâ=â0.0004, ORâ=â0.495) and allele G (Pâ=â0.001, ORâ=â0.596) of rs11564475 in the CTNNB1 gene were correlated with HCC compared with N-HCC patients. These findings were consistent in dominant and recessive models. Multidimensionality reduction analysis revealed that interactions among rs3864004, rs11564475, and rs4730775 were significantly associated with HCC compared with N-HCC patients. The polymorphism rs4135385 of CTNNB1 genotype GA was associated with a higher risk for Stage III + IV HCC (modified Union for International Cancer Control) (Pâ=â0.001, ORâ=â2.238).Genetic polymorphisms in the WNT2 and CTNNB1 genes were closely associated with HCC risk and progression in a Chinese Han population.
Asunto(s)
Pueblo Asiatico/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteína wnt2/genética , beta Catenina/genética , Adulto , Anciano , Alelos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/etnología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Genotipo , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/genética , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/genética , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/etnología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Vía de Señalización Wnt/genéticaRESUMEN
BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF. METHODS: A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR) has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes. RESULTS: This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF. CONCLUSION: This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice.