Acylated Aminooligosaccharides with Inhibitory Effects against α-Amylase from Streptomyces sp. HO1518

Abstract

Five new acylated aminooligosaccharides (1–5), together with one known related analogue (6), were isolated from Streptomyces sp. HO1518. Their structure was identified by extensive spectroscopic analysis, including 1D and 2D NMR data and high resolution electrospray ionization mass spectrometry (HRESIMS), and by comparison with those reported in the literature. All of the new compounds showed more promising porcine pancreatic α-amylase (PPA) inhibitory activities than the clinical drug acarbose, indicating them as potential pharmaceutical drug leads toward type II diabetes.

Acylated Aminooligosaccharides from the Yellow Sea Streptomyces sp. HO1518 as Both α-Glucosidase and Lipase Inhibitors

“…Firstly, 1 – 4 were evaluated for their inhibitory effects on PPA with acarbose as the positive control. Similar to 5 – 8 [ 24 ], 1 – 4 also caused remarkable inhibition of PPA with the IC 50 values ranging from 0.04 to 0.34 μM as shown in Table 3 , of which D 6- O -isobutyryl-acarviostatin II03 ( 3 ) was 77-fold stronger than acarbose (3.80 μM). Subsequently, all of the tested isolates ( 1 – 8 ) showed more potential sucrase inhibition ability than acarbose with the IC 50 values ranging from 0.41 to 9.34 μM.…”

“…The location of the isobutyryloxyl group was assigned at C- D 6 due to the diagnostic ESIMS/MS fragment ions at m / z 1347 (y8), 1202 (y7), 1040 (y6), 1001 (b6), 882 (y5), and 769 (b5) ( Figure 4 ). Likewise, the almost identical coupling constants of the anomeric protons in conjunction with the NOESY correlations ( Figure S54 ) suggested the glycosidic bonds of 3 to be α-(1→4), further evidenced by the chemical conversation between 3 and co-occurring known acarviostatin II03 10 [ 24 ] . Consequently, compound 3 was identified and named D 6- O -isobutyryl-acarviostatin II03.…”

“…Careful comparison of NMR data of 1 with those of previously reported from Streptomyces sp. HO1518 [ 24 ], 1 was inferred as an aminooligosaccharide derivative, which was characterized by acarviosin moiety with d -glucose units attached in the reducing terminus through the glycosidic bond. The reducing terminal glucose unit (ring A) was confirmed by the typical protons of H- A 1α, H- A 1β and H- A 2β (δ H 5.24, 4.66 and 3.28), while the chemical shift of three low-field protons (δ H 5.42, 3H, overlapped) allowed for the assignment of the anomeric protons of rings B–D [ 27 ].…”

“… a Values are expressed as the mean ± SD; b the IC 50 values against PPA for 5 – 8 have been reported in our previous study [ 24 ]; n.t. means not tested.…”

“…Previously, we reported five new acylated oligosaccharides from the Streptomyces sp. HO1518, isolated from a sediment sample of Yellow Sea, among which D6-O-acetylacarviostatin II03 (8) was the most potent α-amylase inhibitor, with an IC50 value 540-fold stronger than acarbose [24]. Very recently, driven by the knowledge of α-glucosidase inhibition in diabetes and obesity [25,26], we tried to test 8 for its inhibitory capacity toward lipase enzyme.…”