Aromatic Acids and Leucine Derivatives Produced from the Deep-Sea Actinomycetes Streptomyceschumphonensis SCSIO15079 with Antihyperlipidemic Activities

Abstract

Six new aromatic acids (1-6) and three new leucine derivatives containing an unusual oxime moiety (7-9) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (10-11). The structures of 1-9 including absolute configurations were determined by detailed NMR, MS, and experimental and calculated electronic circular dichroism spectroscopic analyses. Compounds 1-9 were evaluated for their antimicrobial and cytotoxicity activities, as well as their effects on intracellular lipid accumulation in HepG2 cells. Compounds 3 and 4, with the most potent inhibitory activity on intracellular lipid accumulation at 10 μM, were revealed with potential antihyperlipidemic effects, although the mechanism needs to be further studied.

Keywords: antihyperlipidemic; aromatic acids; deep-sea actinomycetes; oximes.

Figure 1

Structures of compounds 1–11.

Figure 2

Key COSY and HMBC correlations in 1 and 7.

Figure 3

Experimental ECD spectra of 5, and the calculated ECD spectra of truncated models 5a/5b.

Figure 4

Effects of 1–9 on oleic acid-elicited intracellular lipid accumulation. (A) Cell viability of 3, 4, and lovastatin in HepG2 cells; (B) HepG2 cells were treated with isopropanol and intracellular lipid levels were measured using the absorbance at OD 510 nm; (C) Oil Red O staining showed lipid accumulation that was observed with a microscope (scale bar = 1 mm). Data were represented as the mean ± SEM of three in dependent experiments. **** p < 0.001, test group vs. model group.