RESUMO
Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore-based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC50 values against human cancer cell lines MV4-11, A375, and HeLa were 4.2, 7.1, and 11.6 µm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound-healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5.
Assuntos
Antineoplásicos/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas Nucleares/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Área Sob a Curva , Sítios de Ligação , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Descoberta de Drogas , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Proteínas Nucleares/metabolismo , Estrutura Terciária de Proteína , Curva ROC , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Fatores de Transcrição/metabolismoRESUMO
Based on thermodynamic principle, the critical relative humidity of electrolytes is closely related to their solubility. The authors explored the relationship theoretically and calculated critical relative humidity of 21 electrolytes from their solubility in the light of Raoult's law and extended Wilson model. The results indicate that the critical relative humidity values calculated by Raoult's law can not accord with the reported ones and there is a systematic error in the high concentration range; while these calculated by extended Wilson model are comparable to the reported ones.
Assuntos
Eletrólitos/química , Umidade , Solubilidade , Modelos QuímicosRESUMO
According to thermodynamic principle, the critical relative humidity of electrolytes is closely related to their solubility. The authors explored the relationship theoretically and calculated the critical relative humidity of 21 electrolytes in the light of Raoult's law, modified Debye-Hückel model and extended non-random two liquid (NRTL) model from their solubility. The results indicate that the critical relative humidity values calculated by Raoult's law can not accord with the reported ones and there is a systematic error in high concentration range; the values calculated by modified Debye-Hückel model still can not accord with the reported ones well although without systematic error; and the values calculated by extended NRTL are comparable to the reported ones.
