Isolation, Purification, and Characterization of Five Active Diketopiperazine Derivatives from Endophytic SUK 25 with Antimicrobial and Cytotoxic Activities.

In our search for new sources of bioactive secondary metabolites from sp., the ethyl acetate extracts from endophytic SUK 25 afforded five active diketopiperazine (DKP) compounds. The aim of this study was to characterize the bioactive compounds isolated from endophytic SUK 25 and evaluate their bioactivity against multiple drug resistance (MDR) bacteria such as and 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 SUK 25 produces four active DKP compounds and an acetamide derivative, which were elucidated as -(-Val--Pro), -(-Leu--Pro), -(-Phe--Pro), -(-Val--Phe), and -(7-hydroxy-6-methyl-octyl)-acetamide. These active compounds exhibited activity against methicillin-resistant S. aureus ATCC 43300 and , with low toxicity against human hepatoma HepaRG cells. Endophytic SUK 25 has the ability to produce DKP derivatives biologically active against some MDR bacteria with relatively low toxicity against HepaRG cells line.