In searching for symbionts derived from bioactive natural products, six sulfureous diketopiperazines designated as lasiodiplines A-F (1-6) were characterized from the culture of Lasiodiplodia pseudotheobromae F2, previously residing in the apparently normal flower of Illigera rhodantha (Hernandiaceae). Identification of structures was accomplished by a combination of spectroscopic and computational approaches, in conjunction with the low-temperature (100K) single-crystal X-ray diffraction with Cu Kα radiation. Lasiodipline E (5) was demonstrated to be antibacterial against the clinical strains Streptococcus sp., Bacteroides vulgates, Peptostreptococcus sp. and Veillonella parvula, respectively, with an minimum inhibitory concentration (MIC) range of 0.12-0.25 μg/mL. In addition, compounds 4 and 6 exemplify two unusual architectures of natural cyclodipeptides, signifying the unique biochemical characteristics of the producing fungus.
In our search for new sources of bioactive secondary metabolites from Streptomyces sp., the ethyl acetate extracts from endophytic Streptomyces SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic Streptomyces SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as Enterococcus raffinosus, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter spp., and their cytotoxic activities against the human hepatoma (HepaRG) cell line. The production of secondary metabolites by this strain was optimized through Thornton's medium. Isolation, purification, and identification of the bioactive compounds were carried out using high-performance liquid chromatography, high-resolution mass liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance, and cryopreserved HepaRG cells were selected to test the cytotoxicity. The results showed that endophytic Streptomyces SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as cyclo-(L-Val-L-Pro), cyclo-(L-Leu-L-Pro), cyclo-(L-Phe-L-Pro), cyclo-(L-Val-L-Phe), and N-(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and Enterococcus raffinosus, with low toxicity against human hepatoma HepaRG cells. Endophytic Streptomyces SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line.