RESUMO
Amide compounds are important organic compounds, which play an important role in biomedical chemistry, materials science, life science, and other fields. The synthesis of α-CF3 amides, especially compounds containing 3-(trifluoromethyl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepine-2-one, has long been a challenge due to the tensile properties and instability of the rings. Here, we report an example of palladium-catalyzed carbonylation of CF3-containing olefin to form α-CF3 acrylamide. By controlling the ligands, we can get different amide compounds as products. This method has good substrate adaptability and functional group tolerance.
RESUMO
ß-Lactam compounds play a key role in medicinal chemistry, specifically as the most important class of antibiotics. Here, we report a novel one-step approach for the synthesis of α-(trifluoromethyl)-ß-lactams and related products from fluorinated olefins, anilines and CO. Utilization of an advanced palladium catalyst system with the Ruphos ligand allows for selective cycloaminocarbonylations to give diverse fluorinated ß-lactams in high yields.
RESUMO
OBJECTIVE: To explore the function of circular RNA IQ motif-containing GTPase-activating protein 1 (circ-IQGAP1) in interleukin (IL)-1ß-induced osteoarthritis (OA) model and to explore whether circ-IQGAP1 can modulate microRNA-671-5p (miR-671-5p) and transcription factor 4 (TCF4) to regulate chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. METHODS: The cartilage tissues were collected from 32 OA patients or normal subjects. Human chondrocyte CHON-001 cells were challenged via different doses of IL-1ß for 24 hours. CHON-001 cells were transfected with circ-IQGAP1 overexpression vector, TCF4 overexpression vector, small interfering RNA (siRNA) for circ-IQGAP1, miR-671-5p mimic, miR-671-5p inhibitor or corresponding negative controls. Circ-IQGAP1, miR-671-5p and TCF4 abundances in cartilage tissues or CHON-001 cells were examined via quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell viability was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). Cell apoptosis was measured by flow cytometry. The inflammatory injury was analyzed by the secretion levels of inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor-α [TNF-α]) by enzyme-linked immunosorbent assay (ELISA). The extracellular matrix degradation was evaluated by expression of aggrecan and matrix metalloproteinase 13 (MMP13) via western blot. The target relationship of miR-671-5p and circ-IQGAP1 or TCF4 was analyzed via dual-luciferase reporter and RNA immunoprecipitation (RIP) analyses. RESULTS: Circ-IQGAP1 abundance was enhanced in the cartilage tissues from OA patients compared with normal subjects (n = 32), and its expression was increased in CHON-001 cells after treatment of IL-1ß in a dose-dependent pattern. MiR-671-5p expression was decreased in the cartilage tissues from OA patients (n = 32) and IL-1ß-challenged CHON-001 cells. MiR-671-5p expression was negatively associated with circ-IQGAP1 level in OA patients. Circ-IQGAP1 silence mitigated IL-1ß-caused chondrocyte viability reduction, apoptosis promotion, secretion of inflammatory cytokine (IL-6, IL-8 and TNF-α), and extracellular matrix degradation (reduction of aggrecan and increase of MMP13). MiR-671-5p was targeted and inhibited via circ-IQGAP1. MiR-671-5p knockdown attenuated the influence of circ-IQGAP1 interference on IL-1ß-caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. TCF4 was targeted via miR-671-5p, and TCF4 expression was increased in the cartilage tissues from OA patients (n = 32) and IL-1ß-challenged CHON-001 cells. TCF4 abundance in OA patients was negatively correlated with miR-671-5p expression. MiR-671-5p overexpression alleviated IL-1ß-mediated chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation via decreasing TCF4 expression. Circ-IQGAP1 silence reduced TCF4 expression via regulating miR-671-5p in IL-1ß-challenged CHON-001 cells. CONCLUSION: Circ-IQGAP1 knockdown attenuated IL-1ß-caused chondrocyte apoptosis, inflammatory injury, and extracellular matrix degradation. Circ-IQGAP1 could regulate miR-671-5p/TCF4 axis to modulate IL-1ß-caused chondrocyte damage. Circ-IQGAP1 might act as a new target for the treatment of OA.
