Streptimidone

Three new compounds, including 6-methoxy-3,4,5,7-tetramethylisochromane-3,8-diol (1), 3,4,5,7-tetramethylisochromane-3,6,8-triol (2), streptimidone derivative (3), along with ten known compounds (4-13) were isolated from theStreptomyces morookaensisstrain Sm4-1986. Their chemical structures were established based on the information from UV, IR, NMR (1H NMR,13C NMR,1H-1H COSY, HSQC, HMBC, NOESY), and mass spectroscopic. Moreover, all the isolated new compounds were evaluated for antibacterial activities (S.aureus,B. cereus, S. epidermidsand methicillin-resistantS. aureus) and their cytotoxicities against MCF-7, A549, Hela tumor cell lines and Marc-145 normal cell line.

Isaria cicadae is one of the fungi used in traditional Chinese medicine with the longest tradition. It is used not only as a herbal medicine but also as a health food in Asia, together with cultured cordyceps and mycelia of the fungus used as substitute. However, the differences in their metabolite are unknown. Using a high-performance liquid chromatography-mass spectrometry (HPLC-MS)-based metabolomic method, we found that the fungus varies in its metabolism during growth on wild insects, artificially raised insects and artificial medium. There were 109 discriminatory metabolites detected in the samples by orthogonal projection to latent structure discriminant analysis and one-way ANOVA. High level of nonribosomal peptides (NRPs) only existed in the insect portions of the wild cordyceps (WI) and cultured cordyceps (CI), revealing that immunostimulation of the host insects enhanced the synthesis of NRPs in the fungus. The finding of a significantly higher level of sphingolipids in both the insect portions (WI, CI) and the coremia of the wild cordyceps (WC) and cultured cordyceps (CC) but not in cultured mycelia (CM) of I. cicadae implies that the immunostimulation of the live insects can induce the fungus to produce more sphingolipids, and this enhanced ability is probably heritable. Apart from NRPs and sphingolipids, the insect portions also contained higher levels of bioactive compounds such as lateritin, anisomycin, streptimidone and ustiloxins. In contrast, the coremium groups (WC, CC) and CM contained 10-fold less NRP but much higher levels of sanative metabolites such as tocotrienol, 3'-deoxy-hanasanagin, γ-aminobutyric acid and phospholipids than the insect portions. The significantly higher content of antioxidants in WC, CC and CM than in WI and CI suggests that environmental oxygen has a significant effect on the metabolites. The temperature stress which the wild cordyceps encounters during growth is responsible for the relatively high content of trehalose. These findings indicate that the immunity of the host insect and growth environment have a strong impact on the metabolomic variation in Isaria cicadae. The variation in metabolites suggests differential utilization value for the insect portions, coremia and mycelia of the fungus.

Microbial-derived natural products provide unique bioactivities and serve as a unique source of drug leads. In the present study, we isolated one new chresdihydrochalcone (1), one new chresphenylacetone (2), and one known streptimidone (3) from Streptomyces chrestomyceticus BCC 24770 using antibacterial activity-guided isolation and purification procedures. We determined their molecular weights using MS and HRMS and elucidated their chemical structures from their 1D and 2D NMR and electronic circular dichroism (ECD) spectra. Compound 1 showed moderate inhibitory activities against the Gram-positive bacteria Methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus. Cytotoxicity and hemolytic activity were not observed at a concentration of up to 100 μg ml-1. The specific antimicrobial activity and low toxicity of compound 1 indicate this compound to be a potential antibiotic candidate, especially as antibiotic resistance has become a significant public health threat.