RESUMO
Bislangduoids A and B, a novel class of dimeric diterpenoids based on ent-abietanes tethered by C-17-C-15' bridge, were identified as trace components from a traditional Chinese medicine Euphorbia fischeriana (Langdu). Bislangduoid A features a highly oxidized scaffold incorporating a cage-like pentacyclic core. Their structures were elucidated by extensive spectroscopic techniques, electronic circular dichroism, and NMR calculations. The biosynthetic pathway for the dimeric skeleton and the unique caged moiety via Michael and acetal-formation reactions was proposed. Bislangduoid A showed pronounced cytotoxicity against HepG2 cells through the mitochondria-dependent apoptosis pathway.
Assuntos
Antineoplásicos , Diterpenos , Euphorbia , Abietanos/química , Abietanos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Euphorbia/química , Estrutura Molecular , Raízes de Plantas/química , PolímerosRESUMO
Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3ß-hydroxy-25-anhydro-alisol F (1) and 3ß-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC50 values of 10.06 and 30.45 µM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a Ki value of 5.13 µM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids.
Assuntos
Alisma/química , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/antagonistas & inibidores , Triterpenos/farmacologia , Inibidores Enzimáticos/química , Epóxido Hidrolases/química , Concentração Inibidora 50 , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Farmacocinética , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Conformação Proteica , Triterpenos/químicaRESUMO
PURPOSE: This study aims to analyze the clinical-pathological characteristics of multifocal and multicentric breast cancer (MMBC) in Chinese women. METHODS: Sixty-seven cases with MMBC were randomly collected and reviewed at seven hospitals in representative districts of China during 1999 to 2008. RESULTS: The incidence of MMBC in breast cancer in China was 1.75%. Compared to those with unifocal breast cancer, women with MMBC were more likely to have larger tumor size, lymph node metastasis (59.70% vs. 45.62%) and stage III to IV (46.26% vs. 21.10%). The peak age at onset of MMBC was 40 to 49 years old and has been gradually increasing during 1999 to 2008. Most of the MMBC women were treated with surgery and adjuvant therapy. CONCLUSION: In China, the incidence of MMBC in breast cancer is significantly lower than that in Western countries. Compared to unifocal breast cancer, MMBC is biologically more aggressive. Most MMBC women underwent mastectomy, instead of breast conservation surgery.
