RESUMO
A general γ-C(sp2)-H iodination method directed by an aliphatic keto group has been developed under transition-metal-free conditions for the first time, generating iodoarenes in good to excellent yields with excellent site selectivity. This protocol features a wide range of aryl-substituted ketones, short reaction times, mild reaction conditions, and scalable synthetic procedures. A possible reaction mechanism was also proposed based on several control experiments.
RESUMO
The key functions of microtubules and the mitotic spindle in cell division make them attractive targets for cancer therapy. In this study, a series of 1-(benzofuran-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole derivatives was synthesized, and their antiproliferative activities against HCT116, HeLa, HepG2, and A549 cells were evaluated. 6-Methoxy-N-phenyl-3-(4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazol-1-yl)benzofuran-2-carboxamide (17g) exhibited the strongest antiproliferative activities, with IC50 values ranging from 0.57 to 5.7⯵M. Mechanistic studies showed that 17g inhibited tubulin polymerization, leading to the disruption of mitotic spindle formation, cell cycle arrest in the G2/M phase, and apoptosis of A549 cells. A docking study indicated that 17g was a good molecular fit at the colchicine binding site of tubulin. These results showed that 17g is a potential anticancer compound that is worthy of further development as a tubulin polymerization inhibitor.
Assuntos
Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Triazóis/farmacologia , Tubulina (Proteína)/metabolismo , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzofuranos/síntese química , Benzofuranos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Polimerização/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/químicaRESUMO
A p-toluenesulfonic acid catalyzed fluorination of α-branched ketones for the construction of fluorinated quaternary carbon centers has been developed, featuring a broad substrate scope, environmentally benign reaction conditions, and operational simplicity.
RESUMO
BACKGROUND: This study aimed to assess the efficacy and safety of atropine 0.5% eyedrops (ATE) for the treatment of children with low myopia (LM). METHODS: In this study, a total of 126 children with LM were randomly divided into an intervention group (administered 0.5% ATE) and a control group (administered a placebo), with 63 children in each group. The outcome measurements were changes in the spherical equivalent (SE), and axial length (AL), as well as adverse events (AEs). RESULTS: Compared with placebo, administration of 0.5% ATE led to less progression in LM, as measured by SE, and less increase in AL (Pâ<â.01). In addition, no serious AEs occurred in both the groups. CONCLUSION: About 0.5% ATE was efficacious and safe for controlling myopia in children with LM.