Departamento de Ciências Farmacêuticas, Universidade de São Paulo, Avenida do Café, s/n, CEP 14040-903, Ribeirão Preto, São Paulo, Brasil.
Nat Prod Res. 2012;26(23):2168-75. doi: 10.1080/14786419.2011.647020. Epub 2012 Jan 12.
From cultures of thermophilic soil fungus Humicola grisea var thermoidea, a δ-lactam derivative (3-(2-(4-hydroxyphenyl)-2-oxoethyl)-5,6-dihydropyridin-2(1H)-one) that displayed anti-allergic activity was isolated, which was predicted by in silico computational chemistry approaches. The in vitro anti-allergic activity was investigated by β-hexosaminidase release assay in rat basophilic leukaemia RBL-2H3 cells. The δ-lactam derivative exhibited similar anti-allergic activity (IC(50) = 18.7 ± 6.7 µM) in comparison with ketotifen fumarate (IC(50) = 15.0 ± 1.3 µM) and stronger anti-allergic activity than azelastine (IC(50) = 32.0 µM). Also, the MTT cytotoxicity assay with RBL-2H3 cells showed that δ-lactam does not display cytotoxicity at concentrations lower than 50 µM. This study suggests that the δ-lactam derivative has the potential to be used as a lead compound in the development of anti-allergic drugs for clinical use in humans.
从嗜热土壤真菌灰绿青霉中分离出一种 δ-内酰胺衍生物（3-(2-(4- 羟基苯基)-2-氧代乙基)-5,6-二氢吡啶-2(1H)-酮），其具有抗过敏活性，这是通过计算化学方法预测的。通过体外抗过敏活性研究，β-己糖胺酶释放试验在大鼠嗜碱性白血病 RBL-2H3 细胞中进行。与富马酸酮替芬（IC50=15.0±1.3μM）相比，δ-内酰胺衍生物具有相似的抗过敏活性（IC50=18.7±6.7μM），比氮卓斯汀（IC50=32.0μM）具有更强的抗过敏活性。此外，用 RBL-2H3 细胞进行 MTT 细胞毒性试验表明，δ-内酰胺在低于 50μM 的浓度下不显示细胞毒性。这项研究表明，δ-内酰胺衍生物有潜力成为开发用于人类临床的抗过敏药物的先导化合物。
