Inhibition of BACE1 and amyloid β aggregation by polyketide from Streptomyces sp.

• DOI: 10.1111/cbdd.13980
• Publication Date: 2021-11-10T16:57:57Z
• Authors: Masashi Yokoya; Keiyo Nakai; Miki Kawashima; Sanae Kurakado; Natchanun Siriman...; Yoshihiro Kino; Takashi Sugita; Shinya Kimura; Masamichi Yamanaka; Naoki Saito
• Keywords: IC50; Amyloid (mycology)

Alzheimer's disease (AD) causes cognitive impairment in the elderly and is a severe problem worldwide. One of major reasons for pathogenesis AD thought to be due accumulation amyloid beta (Aβ) peptides that result neuronal cell death brain. In this study, bioassay-guided fractionation was performed develop seed compounds anti-AD drugs can act as dual inhibitors BACE1 Aβ aggregation from secondary metabolites produced by Streptomyces sp. To improve solubility, crude extracts were methylated with trimethylsilyl (TMS) diazomethane then purified yield polyketides 1-5, including new compound 1. We synthesized 6 7 (original 2 3, respectively), their activities evaluated. KS-619-1, demethylated form 4 5, isolated evaluated its inhibitory activity. The IC50 values found 0.48 1.1 μM, respectively, indicating KS-619-1 could lead development therapeutic agents AD.