海洋来源链霉菌FIM090041产生的神经氨酸酶抑制剂

摘要

Objective To screen for neuraminidase inhibitors and find out the potential anti-influenza lead compounds. Methods An HTS method was used to screen neuraminidase inhibitors from marine derived microorganisms. The compounds with anti-neuraminidase activities were purified by several chromatographic procedures. The structures were identified by modem spectroscopic methods including UV, MS and NMR spectra. Results Two indole alkaloids, compound 1 (IC50 = 67.8umol/L, Ki=13.5umol/L) and compound 2 (IC50=122.8umol/L, Ki=21.6umol/L), were isolated from the fermentation broth and determined to be identical with SF2583 A and SF2583 B. Conclusion The inhibitory activities to neuraminidase of the two indole alkaloids were firstly reported.%目的 筛选神经氨酸酶抑制剂,发现潜在的抗流感药物先导化合物.方法 利用神经氨酸酶抑制剂高通量筛选方法,从海洋微生物菌库中筛选产生神经氨酸酶抑制剂的菌株,采用多种色谱技术分离纯化获得活性化合物,通过紫外、质谱、核磁共振等现代波谱学方法鉴定其结构.结果 分离到两个吲哚生物碱类活性化合物1和化合物2,结构解析确定它们分别与SF2583 A和SF2583 B同质,对神经氨酸酶的IC50为67.8μmol/L和122.8μmol/L,Ki为13.5μmol/L和21.6μmol/L.结论 本文首次报道该化学结构类型化合物对神经氨酸酶具有一定的抑制作用.