α-Glucosidase Inhibitors from Two Mangrove-Derived Actinomycetes.

α-Glucosidase (AGS) inhibitors have been regarded as an ideal target for the management of type 2 diabetes mellitus (T2DM) since they can maintain an acceptable blood glucose level by delaying the digestion of carbohydrates and diminishing the absorption of monosaccharides. In the process of our endeavor in mining AGS inhibitors from natural sources, the culture broth of two mangrove-derived actinomycetes sp. WHUA03267 and sp. WHUA03072 exhibited an apparent inhibitory activity against AGS. A subsequent chemical investigation into the two extracts furnished 28 secondary metabolites that were identified by spectroscopic methods as two previously undescribed linear polyketides -, four benzenoid ansamycins -, fourteen cyclodipeptides -, one prenylated indole derivative , two fusicoccane-type diterpenoids -, two hydroxamate siderophore -, and five others -. Among all of the isolates, and were obtained from actinomycetes for the first time, while - had never been reported to occur in a marine-derived microorganism previously. In the in vitro AGS inhibitory assay, compounds , , , , , , and exhibited potent to moderate activity with IC values ranging from 35.76 ± 0.40 to 164.5 ± 15.5 μM, as compared with acarbose (IC = 422.3 ± 8.4 μM). The AGS inhibitory activity of , , , , and was reported for the first time. In particular, autolytimycin () represented the first ansamycin derivative reported to possess the AGS inhibitory activity. Kinetics analysis and molecular docking were performed to determine the inhibition types and binding modes of these inhibitors, respectively. In the MTT assay, , , , , , , and exhibited no apparent cytotoxicity to the human normal hepatocyte (LO2) cells, suggesting satisfactory safety of these AGS inhibitors.