Cytotoxic Bagremycins from Mangrove-Derived Streptomyces sp. Q22.

Abstract

New bagremycins C-E (3-5) and bagrelactone A (6), together with known bagremycins A (1) and B (2), 4-hydroxystyrene (7), and 4-hydroxystyrene 4-O-α-d-galactopyranoside (8), were isolated from a mangrove-derived actinomycete, Streptomyces sp. Q22. Structures of these new compounds were elucidated based on their NMR and HRESIMS spectroscopic data as well as chemical degradation. Bagremycin C (3) is a unique analogue with an N-acetyl-(S)-cysteine moiety, while bagrelactone A (6) represents the first example of this type of bagremycin-derived macrolide. Bagremycin C (3) was active against four glioma cell lines, with IC50 values in the range from 2.2 to 6.4 μM, induced apoptosis in human glioma U87MG cells in a dose- and time-dependent manner, and arrested the U87MG cell cycle at the G0/G1 phase.