RESUMO
Vasculogenic mimicry (VM) is the formation of microvascular channels by cancer cells. VM requires cellular processes that are regulated by changes in cellular migration and morphology. Cofilin (CFL), a key regulator of actin depolymerization, has been reported to affect malignant phenotypes of cancer. We show that treatment with inhibitors of actin dynamics suppresses VM in MDA-MB-231 human breast cancer cells. We established CFL-knockout (KO) MDA-MB-231 cells and found that VM was attenuated in CFL-KO cells. Although the re-expression of wild-type CFL restored VM in CFL-KO cells, inactive phosphomimetic CFL failed to do so. Collectively, our results demonstrate that CFL is a critical regulator of VM and implicate CFL as a novel therapeutic target for breast cancer.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Citoesqueleto de Actina , Fatores de Despolimerização de Actina , Actinas , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Neovascularização Patológica/genéticaRESUMO
Iridium-catalyzed reductive nucleophilic addition to N-methoxyamides is reported. The reaction took place in high yields in the presence of a variety of sensitive functional groups such as esters and nitro groups. Mechanistic studies revealed that the reaction of N-methoxyamides proceeded without equilibrium to an enamine intermediate in contrast to that with tert-amides.
Assuntos
Amidas/química , Amidas/síntese química , Irídio/química , Catálise , Ésteres , Estrutura Molecular , EstereoisomerismoAssuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Anti-Inflamatórios/efeitos adversos , Dexametasona/efeitos adversos , Injúria Renal Aguda/sangue , Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-IdadeRESUMO
As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.
