Bioactive Naphthoquinone and Phenazine Analogs from the Endophytic Streptomyces sp. PH9030 as α-Glucosidase Inhibitors

A talented endophytic Streptomyces sp. PH9030 is derived from the medicinal plant Kadsura coccinea (Lem.) A.C. Smith. The undescribed naphthoquinone naphthgeranine G (5) and seven previously identified compounds, 6-12, were obtained from Streptomyces sp. PH9030. The structure of 5 was identified by comprehensive examination of its HRESIMS, 1D NMR, 2D NMR and ECD data. The inhibitory activities of all the compounds toward alpha-glucosidase and their antibacterial properties were investigated. The alpha-glucosidase inhibitory activities of 5, 6, 7 and 9 were reported for the first time, with IC50 values ranging from 66.4 +/- 6.7 to 185.9 +/- 0.2 mu M, as compared with acarbose (IC50 = 671.5 +/- 0.2 mu M). The molecular docking and molecular dynamics analysis of 5 with alpha-glucosidase further indicated that it may have a good binding ability with alpha-glucosidase. Both 9 and 12 exhibited moderate antibacterial activity against methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentration (MIC) values of 16 mu g/mL. These results indicate that 5, together with the naphthoquinone scaffold, has the potential to be further developed as a possible inhibitor of alpha-glucosidase.