RESUMO
A traditional Chinese medicine ingredient, dendrobine, has been demonstrated to have anti-inflammatory properties. However, due to its poor anti-inflammatory properties, its clinical use is limited. Consequently, we have designed and synthesized 32 new amide/sulfonamide dendrobine derivatives and screened their anti-inflammatory activities inâ vitro. Experiments showed that nitric oxide (NO) generation in lipopolysaccharide (LPS)-induced RAW264.7 cells was strongly reduced by derivative 14, with an IC50 of 2.96â µM. Western blot research revealed that 14 decreased the concentration-dependent expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS). Molecular docking was used to predict the binding of the inflammation-associated proteins COX-2 and INOS to compound 14.
Assuntos
Amidas , Ciclo-Oxigenase 2 , Lipopolissacarídeos , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Sulfonamidas , Animais , Camundongos , Células RAW 264.7 , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Relação Estrutura-Atividade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Estrutura Molecular , Relação Dose-Resposta a Droga , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/químicaRESUMO
Hepatocellular carcinoma (HCC), the most common malignancy of the liver, exhibits high recurrence and metastasis. Structural modifications of natural products are crucial resources of antitumor drugs. This study aimed to synthesize C-14 derivatives of tetrandrine and evaluate their effects on HCC. Forty C-14 sulfonate tetrandrine derivatives were synthesized and their in vitro antiproliferative was evaluated against four hepatoma (HepG-2, SMMC-7721, QGY-7701, and SK-Hep-1) cell lines. For all tested cells, most of the modified compounds were more active than the lead compound, tetrandrine. In particular, 14-O-(5-chlorothiophene-2-sulfonyl)-tetrandrine (33) exhibited the strongest antiproliferative effect, with half-maximal inhibitory concentration values of 1.65, 2.89, 1.77, and 2.41 µM for the four hepatoma cell lines, respectively. Moreover, 33 was found to induce apoptosis via a mitochondria-mediated intrinsic pathway via flow cytometry and western blotting analysis. In addition, colony formation, wound healing, and transwell assays demonstrated that 33 significantly inhibited HepG-2 and SMMC-7721 cell proliferation, migration, and invasion, indicating that it might potentially be a candidate for an anti-HCC therapy in the future.
RESUMO
To optimize the configuration of the conventional SE and FSE sequence parameters in low field MRI. With the combination of larger vision, relatively thinner slice thickness, small number of excitation (NEX = 1 or 2), the signal-to-noise ration and the spatial resolution on follow-up images are moderate, the scan time is significantly shorter along with fewer motion artifacts, the check success rate is improved.